Shell Of Nucleus Accumbens


RU-43044 inhibited METH-induced increases in extracellular dopamine (DA), but not serotonin (5-HT), levels in the prefrontal cortex, but did not affect METH-induced increases in extracellular DA levels in the nucleus accumbens Shell, although it inhibited increases in extracellular 5-HT levels.  

OBJECTIVES: The purpose of the present study was to begin bridging the behavioral and tissue studies by microinjecting drugs directly into NAc medial Shell and assessing behavioral effects in free-feeding and FR subjects. MATERIALS AND METHODS: Rats were implanted with microinjection cannulae in NAc medial Shell and a subset were implanted with a stimulating electrode in lateral hypothalamus. CONCLUSIONS: Results suggest that FR may facilitate reward-directed behavior via multiple neuroadaptations in NAc medial Shell including upregulation of D-1 DA receptor function involved in the selection and expression of goal-directed behavior, and increased GluR1-mediated activation of cells that inhibit nonreinforced responses..  

However, the role of the core and Shell subregions of the NAC in aversive conditioning remains unclear. Guide cannulae were implanted in rats in the NAC core and Shell. On the next day, dialysis probes were inserted through the guide cannulae into the NAC core and Shell subregions, and the animals were behaviorally tested for fear behavior either in the same context (cage A) or in a novel context (cage B). These findings suggest that DA mechanisms in both the NAC core and Shell may play an important role in the expression of contextual fear memory..  

In mice injected with melanoma cells, the specific binding of [ (125)I]EYWSLAAPQRF-NH(2), an agonist of neuropeptide FF(2) receptors, was increased in several brain areas involved in the rewarding properties of opiates, including the Shell of the nucleus accumbens, the major islands of Calleja, the ventral endopiriform nucleus and the amygdaloid area.  

Receptor autoradiography revealed increases in D(1) receptor levels in the NAcc (Shell), while decreases in D(2) receptor binding were observed in the CPu and NAcc (core).  

The central extended amygdala (EAc) is an ensemble of highly interconnected limbic structures of the anterior brain, and forms a cellular continuum including the bed nucleus of the stria terminalis (BNST), the central nucleus of the amygdala (CeA) and the nucleus accumbens Shell (AcbSh).  

PHA-L-labeled thalamic afferents were heterogeneously distributed throughout the core and Shell regions of nAcb, overlapping regionally with cholinergic somata and dendrites.  

Other brain areas that also selectively demonstrated nicotine-related declines in SPLI content included prefrontal cortex, the nucleus accumbens Shell, and the very posterior caudate.  

The nucleus accumbens is composed of two subterritories, core and Shell, which have different anatomical connections. Here, we tested the hypothesis that stimulation of the nucleus accumbens core and Shell would have different effects on impulsivity. Rats received bilateral stimulation at the level of the nucleus accumbens core or Shell during a reaction time task. Stimulation of the nucleus accumbens core significantly decreased impulsivity, while stimulation of the Shell increased it.  

In the present study, specific impairments in responding for intravenous cocaine (0.3 mg/inf/0.1 ml/5 s) under a fixed-ratio 1 (FR-1) or second-order schedule (FI 15 min (FR10:S)) were investigated following infusion of the dopamine antagonist, alpha-flupenthixol, into either the nucleus accumbens core or Shell. By comparison, blockade of nucleus accumbens Shell dopamine receptors increased cocaine intake under the FR-1 schedule. These results are discussed with reference to a role for nucleus accumbens Shell dopamine in instrumental responding, and a role of nucleus accumbens core dopamine in incentive motivation, perhaps under the control of contextual stimuli..  

Preferential enhancement of dopamine transmission within the nucleus accumbens (NAc) Shell is a fundamental aspect of the neural regulation of cocaine reward. Here, we used fast-scan cyclic voltammetry to examine specific transmission processes underlying cocaine-evoked increases in dopamine transmission within the NAc core and Shell. Cocaine increased dopamine transmission by slowed uptake and increased concentration of dopamine released in the core and Shell. However, an additional increase in the number phasic release events occurred only within the NAc Shell, and this increase was eliminated by inactivation of midbrain dopaminergic neurons. This represents the first evidence that cocaine directly increases the frequency of dopamine release events and reveals that this is responsible for preferentially increased dopamine transmission within the NAc Shell after cocaine administration.  

Here, we examined the influence of DBS of the nucleus accumbens Shell on cocaine priming-induced reinstatement of drug seeking, an animal model of relapse. During the reinstatement phase, DBS was administered bilaterally to the nucleus accumbens Shell through bipolar stainless steel electrodes. DBS of the nucleus accumbens Shell significantly attenuated the reinstatement of drug seeking precipitated by these higher cocaine doses. Thus, DBS of the dorsal striatum had no influence on cocaine reinstatement and DBS of the accumbens Shell did not affect the reinstatement of food seeking. Together, these results suggest that DBS of the nucleus accumbens Shell may be a potential therapeutic option in the treatment of severe cocaine addiction..  

However, NK3 receptors play a role in the regulation of cocaine-induced DA responses in the nucleus accumbens core and Shell subregions.  

Furthermore, in vivo microdialysis showed that URB597 reduced nicotine-induced dopamine elevations in the nucleus accumbens Shell, the terminal area of the brain's mesolimbic reward system.  

nucleus accumbens Shell, basolateral or lateral amygdala, in this regard, did not seem to be involved in retrieval of the MA-CPP memory.  

Immunofluorescence studies showed that N/OFQ preferentially inhibited phospho-Ser40-TH in nucleus accumbens Shell and that in this subregion NOP receptors partly colocalized with either TH or DA D(1) receptor positive structures.  

The core and Shell subregions of the nucleus accumbens receive differential projections from areas of the medial prefrontal cortex that have dissociable effects on impulsive and perseverative responding. Post-training, selective core lesions were achieved with microinjections of quinolinic acid and Shell lesions with ibotenic acid. Neither core- nor Shell-lesioned rats exhibited persistent deficits in simple instrumental behaviour or challenges to behavioural flexibility or inhibitory control. Core lesions potentiated and Shell lesions attenuated the dose-dependent effect of d-amphetamine on increasing anticipatory responses seen in sham rats. These data imply that the accumbens core and Shell subregions do not play major roles in highly-trained task performance or in challenges to behavioural control, but may have opposed effects following d-amphetamine treatment. Specifically, they suggest the Shell subregion to be necessary for dopaminergic activation driving amphetamine-induced impulsive behaviour and the core subregion for the normal control of this behaviour via conditioned influences..  

medial Shell on intravenous nicotine conditioned place preference and conditioned taste aversion were examined in male adult rats. Dopaminergic denervation in accumbens medial Shell was associated with decreased nicotine conditioned place preference. In addition, dopaminergic denervation of accumbens core but not medial Shell abolished conditioned taste aversion for nicotine. We conclude that nucleus accumbens core and medial Shell dopaminergic innervation exert segregated effects on rewarding and aversive effects of nicotine.  

Microinjection of the calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 into the nucleus accumbens (NAcc) Shell impairs expression of the sensitized locomotion and NAcc dopamine (DA) overflow normally observed in psychostimulant-exposed rats. Based on these results, we investigated the effect of NAcc Shell KN-93 on the enhanced amphetamine (AMPH) intake normally observed in AMPH- relative to saline-exposed rats. After 4 days of stable responding, all rats were bilaterally microinjected with KN-93 (1 or 10nmol/0.5mul/side) into the NAcc Shell, 2min prior to the beginning of the self-administration session. Thus, in a manner similar to what has been reported for sensitized locomotion and NAcc DA overflow, these results suggest that inhibiting CaMKII in the NAcc Shell attenuates the enhanced motivation to obtain a drug reinforcer that is normally displayed in AMPH-exposed rats..  

Here, dynamic fluctuations in extracellular dopamine were measured during ICSS in the rat NAc Shell with fast-scan cyclic voltammetry at carbon-fiber microelectrodes.  

Acute or chronic (0.4 mg/kg, sc, once daily for 2 weeks) administration of nicotine elicited increases in extracellular levels of dopamine, dopamine metabolites, norepinephrine, or serotonin in medial prefrontal cortex, nucleus accumbens Shell, and core of rats. Pretreatment with NT69L (1 mg/kg, intraperitoneally, ip) administered 40 min before nicotine injection significantly attenuated the acute nicotine-evoked increases in norepinephrine levels in medial prefrontal cortex, dopamine and serotonin in nucleus accumbens Shell.  

Considerable evidence implicates the mesolimbic dopamine (DA) system in the processing of nicotine's reinforcing properties, specifically the ventral tegmental area (VTA) and the terminal fields of VTA DAergic projections to the "core" (NAcore) and "Shell" (NAShell) subdivisions of the nucleus accumbens (NAc). We report that microinfusions of DA D(1)-like or D(2)-like receptor-specific antagonists into NAcore or NAShell double dissociate the rewarding and aversive properties of systemic or intra-VTA nicotine, and differentially regulate sensitivity to the rewarding properties as well as the motivational valence of either intra-VTA or systemic nicotine administration. Using a place conditioning procedure, NAShell infusions of a D(2)-like receptor antagonist switched the motivational valence of intra-VTA nicotine from aversive to rewarding and potentiated nicotine reward sensitivity to sub-reward threshold intra-VTA nicotine doses. Thus, D(1)-like versus D(2)-like receptors in NAcore versus NAShell subdivisions play functionally dissociable roles in modulating systemic or intra-VTA nicotine motivational processing..  

In the nucleus accumbens Shell, the +/- genotype elevated basal dopamine levels.  

Second, based on previous studies, we propose hypothetical relationships among these substances and the Shell and core subregions of the NAc..  

We investigated the roles of the core and Shell subfields of the nucleus accumbens (NAc) in drug- or foot-shock-induced reactivation of extinguished conditioned place preference (CPP) in morphine-addicted rats. Rats were given electrolytic lesions to either the core or Shell after CPP was established. During the reacquisition of morphine-seeking behaviour, rats in the Shell and sham lesion groups regained their CPP, while the CPP in core lesion rats remained severely impaired. Similarly, foot-shock-induced reactivation of CPP in the core lesion group was significantly lower than that of the Shell and sham lesion groups, and there was no significant difference between these latter groups. Our results demonstrate that NAc core and Shell lesions elicited dissociable effects on reactivation of extinguished CPP in rats, suggesting that the NAc core might play a more important role in resisting reactivation of extinguished CPP in morphine-addicted rats..  

Norepinephrine (NE) and corticotropin-releasing factor (CRF) signaling in the extended amygdala, including the bed nucleus of the stria terminalis, Shell of the nucleus accumbens, and central nucleus of the amygdala, are generally involved in behavioral responses to environmental and internal stressors.  

In the ventral forebrain, sucrose sham licking increased Fos in the bed nucleus of the stria terminalis, central nucleus of amygdala, and the Shell of nucleus accumbens.  

Here we examined the effects of a selective dopamine D1 and D2 receptor blockade in the Shell and core subregion of the NAC on general PIT. Results reveal that PIT, that is, the increase in instrumental responding during presentation of the Pavlovian stimulus, was reduced by microinjections of the dopamine D1 receptor antagonist SCH-23390 and, less pronounced, by microinjections of the dopamine D2 receptor antagonist raclopride into the NAC core or Shell, respectively. Our data suggest that dopamine D1 and D2 receptors in the NAC core and Shell mediate the general activating effects of Pavlovian stimuli on instrumental behavior..  

Cue-induced reinstatement of alcohol-seeking behavior was associated with a three to five-fold increase in p-ERK1/2 IR in the basolateral amygdala and nucleus accumbens Shell.  

We show that acute systemic administration of the alpha7 nAChR agonist SSR180711 (10 mg/kg) result in a significant increase in Fos protein levels in the Shell of nucleus accumbens in wild-type mice, but has no effect in the transgene mice.  

Moderate staining occurred in the lateral posterior nucleus of the thalamus, superficial layers of neocortex, periaqueductal gray, substantia nigra, stria terminalis, nucleus accumbens Shell and tegmental nucleus.  

Here, we assessed whether endogenous dopamine receptor stimulation in nucleus accumbens contributes to both appetitive behavior and fearful behavior that is generated in keyboard manner by local glutamate disruptions at different sites in medial Shell. 6,7-Dinitroquinoxaline-2,3(1H,4H)-dione (DNQX) microinjections (450 ng) locally disrupt glutamate signals in <4 mm(3) of nucleus accumbens, and generate either desire or fear (or both) depending on precise rostrocaudal location in medial Shell. At rostral Shell sites, local AMPA/kainate blockade generates positive ingestive behavior, but the elicited motivated behavior becomes incrementally more fearful as the same microinjection is moved caudally. We report that local dopamine blockade prevented DNQX microinjections from generating appetitive behavior (eating) in rostral Shell, and equally prevented DNQX from generating fearful behavior (defensive treading) in caudal Shell. We conclude that local dopamine is needed to enable disruptions of corticolimbic glutamate signals in Shell to generate either positive incentive salience or negative fearful salience (valence depending on site and other conditions). Thus, dopamine interacts with localization of valence-biased glutamate circuits in medial Shell to facilitate keyboard stimulation of both appetitive and fearful motivations..  

In addition, this incubation period confers to the environment paired with morphine the ability to increase ERK phosphorylation in the Shell (but not the core) of the nucleus accumbens. These data show that, following repeated morphine injections, a drug-free period induces context-dependent phosphorylation of ERK in a specific population of neurons within the nucleus accumbens Shell.  

Thus, in the present study we compared the effect of a single dose of ethanol (1 g/kg, i.p.) on the extracellular levels of monoamines measured by microdialysis in the Shell of nucleus accumbens of University of Chile bibulous (UChB) and University of Chile Abstainer (UChA) rats, bred for 79 and 88 generations to prefer or reject ethanol, respectively.  

Nicotine-induced effects on dopamine in the dorsal and ventral hippocampus (VH), prefrontal and medial temporal cortex, and superior cerebral peduncle were lower in the young than in adult, the same in the ventral tegmental area (VTA) and lateral septal nucleus (LS), and somewhat higher in the nucleus accumbens Shell (NAccS).  

OBJECTIVES: The present study was designed to evaluate potentially unique contributions of the NAC core and Shell to this behavior. Before each test session, neural activity was inhibited selectively in the NAC core or Shell using bilateral microinfusions of the gamma-aminobutyric acid agonists, baclofen and muscimol (0/0 or 1.0/0.1 mM; 0.3 mul per hemisphere). RESULTS: Neural inactivation of the NAC Shell or core attenuated responding in the cocaine context and, interestingly, increased responding in the extinction context.  

However, the extent to which the two subregions of the NAc, the core and Shell, form differentiated circuits within the amygdala- and hippocampal-ventral striatal circuitry remains unclear. The present study investigated the effects of selective excitotoxic lesions of the nucleus accumbens Shell or core subregion on appetitive elemental cue and context conditioning, shown previously to be dependent on the basolateral amygdala and hippocampus, respectively. NAc Shell lesions selectively impaired the acquisition of conditioned place preference and the use of spatial information to retrieve information about a discrete cue, whereas, as expected, NAc core lesions attenuated the acquisition of cue conditioning compared with sham rats. In a subsequent experiment, disconnection of the HPC from the NAc Shell using unilateral asymmetric lesions of each structure resulted in a pattern of impairment in place conditioning and context-dependent cue retrieval similar to that produced by NAc Shell lesions. These data not only suggest that the NAc core and Shell subregions subserve distinct associative processes but also that the NAc Shell and HPC are important functional components of a limbic corticostriatal network involved in spatial context conditioning..  

This study investigated the effect of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 2.5 and 5.0 nmol/side) microinjected into the core and Shell sub-regions of the accumbens (Acb) nucleus, on food intake and the level of anxiety in female rats. Bilateral microinjections of CNQX (5.0 nmol/side) into the Acb Shell (AP, +1.08 to +2.04), but not into the Acb core, induced an anxiolytic-like effect in relation to rats microinjected with vehicle, since the animals exhibited low level of SAP in the feeding test. The anxiolytic-like effect induced by 5.0 nmol CNQX microinjection into the Acb Shell may not be ascribed to changes in the motor activity of the animals, because the frequency of locomotion, rearing and grooming remained unchanged after the drug microinjection. However, neither Acb Shell nor Acb core CNQX microinjections were able to change the animals food intake along 1h feeding behaviour evaluation. Food intake remained unchanged 24h after the drug microinjections either into the Acb Shell or into the Acb core.  

Furthermore, the anticataleptic dose of 8-OH-DPAT showed a regionally specific reduction of haloperidol-induced Fos expression in the dorsolateral striatum (dlST) and the core region of the nucleus accumbens (AcC), without affecting that in the medial prefrontal cortex, the Shell region of the nucleus accumbens or the lateral septal nucleus.  

Infusions of MSX-3 into the nucleus accumbens core increased locomotion in haloperidol-treated rats, but there were no effects of infusions into the accumbens Shell or ventrolateral neostriatum.  

However, recent studies suggest that the effects of opioid drugs on the core subregion of nucleus accumbens may completely differ from those observed in the Shell. We used in vivo microdialysis to simultaneously apply selective mu- and delta-opioid receptor agonists and to measure extracellular levels of dopamine in three subregions of the accumbens, namely Shell, core, and the transition zone between them. The regional analysis of these subregions of the accumbens demonstrated that basal levels of dopamine and its metabolites were higher in the core, and decreased from this subregion to the Shell. However, the application of these drugs to the Shell significantly reduced the dopamine levels in this subregion. Local application of the same doses of these drugs in the transition zone between the Shell and the core did not significantly affect the dopamine levels in dialysates. These results suggest that the opioid circuits modulating dopaminergic activity in the Shell could differ from those in the core of the nucleus accumbens..  

Sweetened milk ingestion was associated with increased numbers of c-Fos positive neurons in the caudal core and Shell of the nucleus accumbens (NAc), the paraventricular thalamus (PVT), central nucleus of the amygdala (CEA), the basal lateral amygdala (BLA), in orexin-A containing neurons of the lateral hypothalamus (LH), and in cocaine and amphetamine regulated transcript (CART) neurons of the arcuate hypothalamus.  

Fos-IR specific to PM self-stimulation was also observed within the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAS)-Shell, but not within NAS-core, caudate putamen, medial prefrontal or orbital cortices. They suggest that among ventral midbrain projection sites, the BNST and NAS-Shell constitute important components of the circuitry implicated in reward.  

Adult male Sprague-Dawley rats received injections of CTAP into the caudate putamen, the rostral or caudal ventral tegmental area (VTA) or the medial Shell or core of the nucleus accumbens prior to cocaine to determine the role of mu opioid receptors in cocaine-induced reward and hyperactivity. Results demonstrate that animals pre-treated with CTAP into the nucleus accumbens core or rostral VTA, but not the caudal VTA, caudate putamen or medial nucleus accumbens Shell, during conditioning with cocaine showed an attenuation of the development of cocaine-induced place preference. In contrast, CTAP injected into the nucleus accumbens Shell but not the core attenuated the expression of cocaine place preference. In addition, the number of cFos positive cells was increased in the motor cortex, medial and ventromedial aspects of the nucleus accumbens Shell, basolateral amygdala and caudal VTA during the expression of cocaine place preference, and this increase was attenuated in the animals that received intra-accumbens core CTAP during daily cocaine conditioning.  

We previously showed that 14 days of daily intramuscular injections of the AAS nandrolone decanoate (15 mg/kg) reduced the extracellular levels of the dopaminergic metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens Shell using microdialysis.  

Consumption of the HP diet increased extracellular DA levels within the nucleus accumbens (NAc) Shell. Increased DA in the NAc Shell was not related to the quantity of the HP diet consumed, and the DA response did not habituate following daily scheduled access to the HP diet. Interestingly, treatment with LY255582 inhibited consumption of the HP diet and the HP diet-associated increase in NAc Shell DA levels.  

A primary efferent projection from the infralimbic cortex is to the nucleus accumbens Shell. Akin to infralimbic cortex, inhibition of the accumbens Shell induced cocaine seeking in extinguished rats. However, bilateral inhibition of the Shell also elicited increased locomotor activity. Nonetheless, unilateral inhibition of the accumbens Shell did not increase motor activity, and simultaneous unilateral inactivation of the infralimbic cortex and Shell induced cocaine seeking, suggesting that an interaction between these two structures is necessary for extinction training to inhibit cocaine seeking. The infralimbic cortex and accumbens Shell appear to be recruited by extinction learning because inactivation of these structures before extinction training did not alter cocaine seeking. Together, these findings suggest that a neuronal network involving the infralimbic cortex and accumbens Shell is recruited by extinction training to suppress cocaine seeking..  

Our findings suggest that 'liking' and 'wanting' are anatomically dissociable: i) the nucleus accumbens contains a highly localized subregion corresponding to the rostro-dorsal quarter of the medial accumbens Shell dedicated to hedonic processing; ii) by contrast, 'wanting' is widely distributed throughout the nucleus accumbens.  

Although cannabinoid-induced behavioral sensitization and cross-sensitization with opiates has been recently demonstrated, no information is available on the associated state and responsiveness of dopamine (DA) transmission in the nucleus accumbens (NAc) Shell and core. In this study we investigate by means of dual probe microdialysis, the effect of exposure to a sensitizing regimen of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and morphine on the extracellular concentrations of DA under basal conditions and after challenge with Delta(9)-THC and morphine in the NAc Shell and core. After 14-20 days from the last injection, the animals were implanted with two microdialysis probes, one aimed at the NAc Shell and the other at the core. Rats pre-exposed to Delta(9)-THC showed behavioral sensitization associated with a reduced stimulation of DA transmission in the NAc Shell and an increased stimulation in the NAc core in response to Delta(9)-THC challenge. Pre-exposure to Delta(9)-THC induced behavioral sensitization to morphine also, but only a reduced stimulation of DA transmission in the NAc Shell was observed. Animals pre-treated with morphine showed behavioral sensitization and differential changes of DA in the NAc Shell and core in response to Delta(9)-THC challenge with a decreased response in the Shell and an increased response in the core.  

Dopamine increases in the nucleus accumbens after ethanol administration in rats, but the contributions of the core and Shell subregions to this response are unclear. However, both the 1.0 g/kg and 1.5 g/kg ethanol infusions produced significant increases in dopamine levels in the Shell that were significantly higher than those in the core. An ethanol dose-response effect on dopamine in the Shell was observed when saline controls, 0.5, 1.0, and 1.5 g/kg groups were compared. For the cumulative-dosing study, the first, second, and fourth infusions resulted in significant increases in dopamine in the Shell. The results of this study show that the Shell has a stronger response than the core to i.v. ethanol, that dopamine in the Shell increases in a dose-dependent manner between 0.5-1.0 g/kg doses, but that the response to higher ethanol doses reaches a plateau..  

To clarify whether the dopaminergic system is involved in the antinociceptive action of N(2)O, saline or raclopride, a dopamine D(2)-like receptor antagonist, was injected into the nucleus accumbens (NAc) Shell region. Raclopride, injected into the NAc Shell region, attenuated the antinociceptive effect of N(2)O in the formalin test, and blocked the suppressive effect of N(2)O on the formalin-induced c-Fos expression in the dorsal horn of the spinal cord by N(2)O. CONCLUSION: It is possible that inhalation of N(2)O activates mesolimbic dopaminergic neurons, and that the antinociceptive effect of N(2)O is at least partially mediated by dopamine D(2)-like receptors in the NAc Shell region..  

Furthermore, A-582941 increased the number of Arc and c-Fos immunopositive cells in the mPFC, VO/LO, and Shell of the nucleus accumbens, in both juvenile and adult rats.  

It has previously been reported that dopamine (DA) responses observed in the core and dorsomedial Shell parts of the nucleus accumbens (Nacc) in latent inhibition (LI) are dependent on the left entorhinal cortex (ENT). In the retention (test) session the results were as follows: (1) pre-exposed (PE) conditioned animals microinjected with TTX, displayed aversion toward the CS; (2) in the core part of the Nacc, for PE-TTX-conditioned rats as for non-pre-exposed (NPE) conditioned animals, DA levels remained close to the baseline whereas DA variations in both groups were significantly different from the DA increases observed in PE-conditioned rats microinjected with the solvent (phosphate-buffered saline (PBS)); (3) in the Shell part of the Nacc, for PE-TTX-conditioned rats, DA variations were close to or above the baseline.  

Neurochemical evaluation demonstrated a reduction in dopamine levels in the caudate-putamen and nucleus accumbens core and Shell as well as an enhanced utilization ratio in the caudate-putamen after both withdrawal periods.  

We investigated whether directly stimulating ionotropic glutamate receptors (GluRs) within the nucleus accumbens core or Shell would differentially influence renewed cocaine-seeking behavior following extinction training. We also tested the hypothesis that GluR1 subunit (GluR1) containing alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) receptors in the nucleus accumbens core and not the Shell regulate reinstatement of previously extinguished cocaine-seeking behavior. Microinjection of AMPA into the nucleus accumbens Shell and the nucleus accumbens core dose-dependently elicited significant cocaine-seeking behavior. Administration of antisense oligonucleotides (AS) directed against GluR1 subunit mRNA into the core and Shell disrupted AMPA- and cocaine-primed reinstatement--with the most pronounced effects seen in the nucleus accumbens Shell. These results demonstrate that GluRs in the nucleus accumbens core and Shell influence AMPA- and cocaine-primed reinstatement, yet the nucleus accumbens Shell exerts a prepotency over the nucleus accumbens core..  

Centrolateral striatum, Shell and core of the nucleus accumbens, paraventricular thalamic nucleus and some layers of motor and somatosensory cortices showed but negligible Fos protein induction in drug-naive rats; this response was markedly enhanced by morphine pretreatment only, which effect might be related to the emergence of opiate addiction.  

Reinstatement of previously extinguished instrumental responding for drug-related cues has been used as an animal model for relapse of drug abuse, and is differentially affected by inactivation of the core and Shell subregions of the nucleus accumbens (NAc). To compare the roles of these subregions in reinstatement induced by cues associated with natural and drug rewards, the present study assessed the effects of inactivation of the NAc core and Shell on cue-induced reinstatement of food-seeking behavior. Following saline infusions into the NAc core or Shell, rats displayed a significant increase in lever pressing during reinstatement sessions. In contrast, inactivation of the Shell had the opposite effect, potentiating responding relative to vehicle treatments. These data suggest that the NAc core and Shell play opposing, yet complementary roles in mediating the influence that food-associated conditioned stimuli exert over behavior. In contrast, the Shell facilitates alterations in behavior in response to changes in the incentive value of conditioned stimuli.  

The functional analogies and our prior results showing apomorphine- and AS-induced relocation of the dopamine D1 receptor (D1R) in the nucleus accumbens (Acb) Shell suggest that apomorphine and AS may affect the subcellular distribution of the NMDA receptor NR1 subunit, a protein that forms protein-protein interactions with the D1R. We quantitatively compared the electron microscopic immunogold labeling for NR1 in dendritic profiles distinguished with respect to presence of D1R immunoreactivity and location in the Acb Shell or core of rats receiving a single s.c. A significantly higher percentage of plasmalemmal and a lower percentage of cytoplasmic NR1 immunogold particles were seen in D1R-labeled dendritic spines in the Acb Shell of the APO+AS group compared with all other groups. D1R-containing small dendrites in the Acb Shell of the APO+AS group also showed a significantly higher density of plasmalemmal and a lower density of cytoplasmic NR1 immunogold particles compared with VEH or APO groups.  

To further address this issue, we undertook a detailed ultrastructural analysis to characterize changes in the subcellular and subsynaptic localization of mGluR1a and mGluR5 in the core and Shell of nucleus accumbens following acute or chronic cocaine administration in rats. After a single cocaine injection (30 mg/kg) and 45 min withdrawal, there was a significant decrease in the proportion of plasma membrane-bound mGluR1a in accumbens Shell dendrites. However, neither acute nor chronic cocaine treatments induced significant change in the localization of mGluR5 in accumbens core and Shell, which is in contrast with the significant reduction of plasma membrane-bound mGluR1a and mGluR5 induced by local intra-accumbens administration of the group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG).  

Furthermore, using an immunofluorescent staining approach, we found that inhibition of ERK activation completely abolished cocaine-induced increase in number of c-Fos-positive cells in the core region of NAc, whereas, in Shell region of NAc, inhibition of ERK activation partially attenuated cocaine-induced c-Fos expression.  

In electrophysiology studies, electrically evoked dopamine release in slice preparations was significantly attenuated in OP rats, not only in the nucleus accumbens but also in additional terminal sites of dopamine neurons such as the accumbens Shell, dorsal striatum, and medial prefrontal cortex, suggesting that there may be a widespread dysfunction in mechanisms regulating dopamine release in this obesity model.  

On the other hand, they were associated with reduced cocaine-induced expression of the immediate early gene zif-268 in the nucleus accumbens (Shell and core) of EE mice.  

An unbiased conditioned place preference paradigm and the microdialysis technique was used to evaluate the effect of (+)-morphine pretreatment on the conditioned place preference produced by (-)-morphine and the increased release of the dopamine produced by mu-opioid ligand endomorphin-1, respectively, in the posterior nucleus accumbens Shell of the male CD rat. (-)-Morphine (2.5-10 microg) microinjected into the posterior nucleus accumbens Shell dose-dependently produced the conditioned place preference. Pretreatment with (+)-morphine (0.1-10 pg) given into the posterior accumbens Shell for 45 min dose-dependently attenuated the conditioned place preference produced by (-)-morphine (5 microg) given into the same posterior accumbens Shell. Thus, like given systemically, (+)-morphine given into the posterior nucleus accumbens Shell also induces a U-shaped dose-response curve for attenuating the (-)-morphine-produced conditioned place preference. Microinjection of mu-opioid agonist endomorphin-1 (1-10 microg) given into the ventral tegmental area dose-dependently increased the release of the extracellular dopamine in the posterior nucleus accumbens Shell in the urethane-anesthetized rats. It is concluded that (+)-morphine attenuates the (-)-morphine-produced conditioned place preference and the mu-opioid receptor-mediated increase of extracellular dopamine in the posterior nucleus accumbens Shell of the rat..  

Infusions of 5 microg/0.3 microl WIN into either NAc (core or Shell), dHIP or VTA did not affect PPI and locomotion immediately afterwards.  

The number of FosB/DeltaFosB-labeled neurons in regions of the frontal cortex, nucleus accumbens (NAc) Shell and core, and in the medial, central and basolateral amygdala increased significantly immediately after the last stress episode, and remained enhanced for 21 days. Prior social defeat stress augmented DAMGO-induced Fos expression in the NAc Shell, suggesting that Fos expression in this region might be the direct result of MOR activity in the VTA.  

METHODS: We determined the basal mRNA and protein levels of BDNF by in situ RT-PCR and immuno-histochemical procedure, respectively, in the amygdaloid [ central nucleus of amygdala (CeA), medial nucleus of amygdala (MeA), and basolateral amygdala (BLA)], nucleus accumbal (NAc Shell and core), and bed nucleus of stria terminalis (BNST) [ lateral BNST (lBNST), medial BNST (mBNST), and ventral BNST (vBNST)] brain structures of P and NP rats. On the other hand, mRNA and protein levels of BDNF were similar in the NAc Shell and core structures of P and NP rats.  

Thus, we examined the behavioral effects of up- and downregulating basal AMPA receptor function in the NAc core and Shell using viral-mediated gene transfer of wild-type glutamate receptor 1 (wt-GluR1) or a dominant-negative pore-dead GluR1 (pd-GluR1), respectively.  

An important role is contributed to individual differences in the reactivity of the: hypothalamic-pituitary-adrenal axes, the reactivity of second messenger systems as well in the aminergic reactivity of the accumbens Shell and core.  

Withdrawal was accompanied by an increase in c-Fos expression in the Acb Shell (AcbSh), which was reduced by SB-334867 but had no effect on the VTA or the LC.  

The present study examined the effect of cocaine withdrawal on subcellular localization of DOR in dendrites of the NAcb core (NAcbC) and Shell (NAcbS) using immunoelectron microscopy.  

In contrast, following a history of dependence, a markedly suppressed c-fos response to acute ethanol was found in the medial pre-frontal/orbitofrontal cortex (OFC), nucleus accumbens Shell (AcbSh) and paraventricular nucleus (PVN).  

This kind of maternal experience-based memory is critically dependent on the mesolimbic dopamine (DA) system, especially the nucleus accumbens (NA) Shell. However, the relative contributions of the two main DA receptor systems (D1 and D2) within the Shell have not been delineated. This study investigates the roles of dopamine D1 and D2 receptors in maternal memory by infusing a selective D1 antagonist, SCH-23390; a selective D2 antagonist, sulpiride; or a combination D-1/D-2 antagonist, cis-Z-flupenthixol, into the NA Shell of postpartum female rats.  

Cocaine and D: -amphetamine appear to be more rewarding when administered into the medial olfactory tubercle or medial accumbens Shell than into their lateral counterparts, including the accumbens core. OBJECTIVES: We sought to determine whether rats self-administer the popular recreational drug (+/-)-3,4-methylenedioxymethamphetamine (MDMA) into ventrostriatal subregions and whether the medial olfactory tubercle and medial accumbens Shell mediate MDMA's positive reinforcing effects more effectively than their lateral counterparts. RESULTS: Rats receiving 30 mM MDMA into the medial olfactory tubercle, medial accumbens Shell, or accumbens core, but not the lateral tubercle or lateral Shell, showed higher self-administration rates than rats receiving vehicle. The medial Shell supported more vigorous self-administration of MDMA at higher concentrations than the core or medial olfactory tubercle. In addition, intra-medial Shell MDMA self-administration was disrupted by co-administration of the D1 or D2 receptor antagonists SCH 23390 (1-3 mM) or raclopride (3-10 mM). The medial accumbens Shell appears to be more important than other ventrostriatal subregions in mediating the positive reinforcing effects of MDMA via both D1- and D2-type receptors.  

Intravenous diphenhydramine (1.0-3.0 mg/kg) (+)- and (-)-chlorpheniramine (1.0-5.6 mg/kg) but not triprolidine (1.0-3.0 mg/kg) elicited a cocaine-like pattern of stimulation of DA transmission with larger effects in the NAc Shell than core.  

PD message was predominantly augmented in the nucleus accumbens, rostral pole, core, and Shell, and the medial aspects of caudate/putamen.  

Ethanol administration increased the number of Fos-immunoreactive cells in the infralimbic (+57.5%) and prelimbic (+105.3%) cortices, nucleus accumbens Shell region (+88.2%), medial part of the central nucleus of the amygdala (+160%), and lateral part of the bed nucleus of the stria terminalis (+198.8%) compared with the water-treated group. In the nucleus accumbens Shell region, central nucleus of the amygdala, and bed nucleus of the stria terminalis, more than 80% of Fos-immunoreactive neurons were GABAergic after ethanol administration.  

The c-fos response to amphetamine in the accumbens core was augmented in amphetamine-pretreated animals with a shift in the distribution of optical density, while no effect of sensitization was seen in the nucleus accumbens Shell or prefrontal cortex.  

At rostral sites of the medial Shell, localized glutamate disruptions typically generate intense appetitive behaviors in rats, but the disruption incrementally generates fearful behaviors as microinjection sites move more caudally. We found that exposure to stressful environments caused caudal fear-generating zones to expand rostrally, filling approximately 90% of the Shell. Conversely, a preferred home environment caused fear-generating zones to shrink and appetitive-generating zones to expand caudally, filling approximately 90% of the Shell.  

Here, we report the identification of a type of dopaminergic neuron within the mesocorticolimbic dopamine system with unconventional fast-firing properties and small DAT/TH mRNA expression ratios that selectively projects to prefrontal cortex and nucleus accumbens core and medial Shell as well as to basolateral amygdala. In contrast, well-described conventional slow-firing dopamine midbrain neurons only project to the lateral Shell of the nucleus accumbens and the dorsolateral striatum.  

Because dopamine in the nucleus accumbens Shell (NAcS) is implicated in food reward, the present study examined whether NAcS D1 or D2 antagonists altered acquisition and/or expression of fructose-CFP.  

The CS+ preference was then evaluated in two-bottle preference tests following bilateral injection of the dopamine D1-like receptor antagonist SCH23390 into the NAc Shell at total doses of 0, 12, 24 and 48 nmol. In Experiment 2, new rats were injected daily in the NAc Shell with either saline or SCH23390 (12 nmol), 10 min prior to training sessions with CS+ with IG glucose and CS- with IG water. These results demonstrate that D1-like receptors in the NAc Shell and core are greatly involved in the acquisition, but less so in the expression, of a flavor preference conditioned by postingestive effects of glucose..  

The resulting anterograde labeling includes the olfactory tubercle, the islands of Calleja and sparse terminal fields in the Shell of the nucleus accumbens and ventral pallidum. The possibility that parts of the accumbens Shell and/or ventral pallidum could be included in the mammalian olfactostriatum cannot be discarded..  

Moreover, CP-55,940 also increased mu-opioid receptor levels in the subcallosal streak of pre-treated animals and decreased mu-opioid receptor functionality in the nucleus accumbens Shell but again, only in males. Our data indicate that adult male rats exposed to the cannabinoid in adolescence self-administer more morphine than females, but only when the demands required by the schedule of reinforcement are low, which might be related to the decrease in mu-opioid receptor functionality in the NAcc-Shell observed in these animals..  

Microdialysis revealed a concomitant increase in extracellular acetylcholine and decrease in dopamine release in the nucleus accumbens Shell.  

Thereafter, changes in the expression of glutamic acid decarboxylase (GAD)67 mRNA were estimated by in situ hybridization in the central nucleus of the amygdala (CeA), basolateral amygdala (BLA), dorsolateral striatum (dLStr), nucleus accumbens Shell (AcS) and core (AcC).  

These include the infralimbic, prelimbic, dorsal agranular insular, and entorhinal cortices, the ventral subiculum of the hippocampus, dorsal tenia tecta, claustrum, lateral septum, dorsal striatum, nucleus accumbens (core and Shell), olfactory tubercle, bed nucleus of stria terminalis (BST), medial, central, cortical, and basal nuclei of amygdala, and the suprachiasmatic, arcuate, and dorsomedial nuclei of the hypothalamus.  

Pretreatment with GTS (100, 200, 400 mg/kg, i.p.) 30 min before the daily injections of cocaine (15 mg/kg, i.p.) significantly inhibited the repeated cocaine-induced increase in locomotor activity as well as the c-Fos expression in the core and Shell in a dose-dependent manner.  

By contrast, infusions of SB-277011-A into the Shell subregion of the nucleus accumbens and also into the dorsal striatum were without effect.  

Immunogold quantification was performed in two distinct Acb subregions, the Shell, an area involved in processing incentive salience related to rewarding stimuli, and the core, an area involved in reward-seeking behaviors. When compared to saline injected animals, morphine produced a decrease in plasma membrane GluR1 labeling in medium- and large-sized D1R expressing dendritic profiles in the Acb Shell. These results indicate that chronic intermittent injection of escalating doses of morphine is accompanied by ultrastructural plasticity of GluR1 in neurons that are responsive to glutamate and dopamine-induced D1R activation in the Acb Shell, and neurons capable of responding to glutamate but not D1R receptor stimulation in the Acb core.  

Shell subregions of this nucleus were apparent for the different drugs.  

We also found that evoked dopamine release is significantly increased in the Acb Shell of MCH-/- mice.  

We show that stimulation of D1-like dopamine receptors in the nucleus accumbens Shell reinstates cocaine seeking by activating L-type Ca(2+) channels and CaMKII. Cocaine reinstatement is associated with D1-like dopamine receptor-dependent increases in accumbens Shell CaMKII phosphorylated on Thr286 and glutamate receptor 1 (GluR1) phosphorylated on Ser831 (a known CaMKII phosphorylation site), in addition to increases in cell-surface expression of GluR1-containing AMPA receptors in the Shell. Consistent with these findings, cocaine reinstatement is attenuated by intra-Shell administration of AAV10-GluR1-C99, a vector that impairs the transport of GluR1-containing AMPA receptors. Thus, CaMKII may be an essential link between accumbens Shell dopamine and glutamate systems involved in the neuronal plasticity underlying cocaine craving and relapse..  

In vitro results show the ability of the CB(1) receptor agonist CP 55,940 to reduce the affinity of D(2) receptor agonist binding sites in both the dorsal and ventral striatum including the nucleus accumbens Shell.  

The purpose of this study was to test whether alcohol-induced dopamine release into the nucleus accumbens (NAc) Shell is modified by different pre-treatments: water (i.g.), alcohol (1 g/kg, i.g.), nicotine (0.4 mg/kg, s.c.), and WIN 55,212-2 (1 mg/kg, s.c.). Finally, a cannula was surgically implanted into the NAc Shell and alcohol-induced extracellular dopamine release was monitored in freely moving rats. These data demonstrate that pre-treatment with nicotine and the cannabinoid agonist WIN 55,212-2 is able to change the sensitivity of the NAc Shell in response to a moderate dose of alcohol.  

In Experiments 2 and 3, AMPH (0.5 microl of 40 microg/microl) or vehicle was infused bilaterally into the Shell region of the nucleus accumbens (NAc) or core region of the NAc, respectively. In Experiments 2 and 3, infusions of AMPH into the NAc Shell or core significantly increased locomotor activity during the open field test but failed to affect most measures of paced mating behavior.  

In the ventral division, the nucleus accumbens, which subserves adaptive and goal-directed behaviors, is further subdivided into Shell and core. Accumbal neurons show different types of experience-dependent plasticity: those in the core seem to discriminate the motivational value of conditioned stimuli, features that rely on the integration of information and enhanced synaptic plasticity at the many spines on these cells, whereas Shell neurons seem to be involved with the release of predetermined behavior patterns in relation to unconditioned stimuli, and the behavioral consequences of repeated administration of addictive drugs. In the core, the principal neurons are medium sized and densely spiny, but in the medial Shell, these same neurons are much smaller and their dendrites, significantly less spiny, suggesting that morphological differences could mediate unique neuroadaptations associated with each region. This review is focused on evaluating the structural differences in nucleus accumbens core and Shell neurons and discusses how such different morphologies could underlie distinguishable behavioral processes..  

In addition to projections to the caudate-putamen, the ventrolateral, lateral and dorsolateral orbital areas have a scarce projection to the most lateral part of the nucleus accumbens Shell in the ventral striatum.  

The present study investigated the release of dopamine from the nucleus accumbens (Shell) in response to pup-stimuli in the absence of lactation and maternal behaviors at time of sample collection.  

In this study, using single-cell juxtacellular labeling with neurobiotin as well as anterograde neuroanatomical tracing with biotinylated dextran amine, we investigated the three-dimensional (3D) organization of dendrites and axons of MSN of the rat Acb in relation to subregional (Shell-core) and compartmental (patch-matrix) boundaries. Our results show that dendritic arbors of MSN in both the Acb Shell and core subregions are preferentially oriented, i.e., they are flattened in at least one of the 3D-planes. The preferred orientations are influenced by Shell-core and patch-matrix boundaries, suggesting parallel and independent processing of information. Dendritic orientations of MSN of the Acb core are more heterogeneous than those of the Shell and the dorsal striatum, suggesting a more complex distribution of striatal inputs within the core. Although dendrites respect the Shell-core and patch-matrix boundaries, recurrent axon collaterals may cross these boundaries.  

Different experimental and biological parameters such as route of administration (ip, sc, iv, local), rat and mouse strains, gender, age aspects, and regions cannulated (NAC core and Shell) were considered. Results from the NAC Shell region displayed greater DA overflow as compared with the NAC core.  

In the expression experiments, mice received bilateral lesions of the Acb, Acb Shell, Acb core, and Amy, or unilateral lesions of the Amy after training but before testing.  

In the following experiments we assessed in the male Wistar rat: (1) whether amphetamine disruption of overshadowing extends to an appetitively motivated overshadowing task; and (2) whether selective electrolytic lesions to the n.acc (Shell versus core subfields) disrupt appetitively motivated overshadowing. The presence of overshadowing was demonstrated as reduced conditioning to the light when it had been previously conditioned in compound compared to when it had been conditioned alone.It was predicted that AMP and lesions to the n.acc Shell would disrupt overshadowing. Contrary to prediction, the Shell lesioned animals did not differ from shams.  

Such individuals tended to express higher PENK mRNA than the 81-bp homozygotes, but PENK levels within the nucleus accumbens (NAc) Shell were most strongly correlated to catecholamine-O-methyltransferase (COMT) genotype.  

Groups ABA and ABB showed test-associated c-Fos induction in prelimbic prefrontal cortex, nucleus accumbens (core, Shell, rostral pole), striatum, lateral amygdala, perifornical hypothalamus, and ventral tegmental area.  

The nucleus accumbens is part of the ventral striatum and is composed of two main regions: core and Shell. Core and Shell share a similar cellular composition, but differ in their connectivity with other brain areas. Considering that the nucleus accumbens is related to motivation and that it receives a strong projection from the basolateral amygdala, we have studied the effect of stimulating accumbens Shell or core on medial perforant path-granule cells' LTP in anesthetized male Wistar rats. We found that electrical stimulation of the Shell enhances the magnitude of LTP while the stimulation of the core completely prevents LTP induction. The stimulation of the accumbens Shell or core alone produced no apparent, direct field potential in dentate gyrus. Additionally, the co-stimulation of the Shell or core with the medial perforant path does not modify the input-output curves obtained using stimulation of the perforant path only. These results demonstrate that electrical stimulation of the accumbens Shell or core has a bidirectional effect on LTP induction at the dentate gyrus..  

The role of orexin receptors in the nucleus accumbens Shell in rat turning behaviour of rats was studied. Unilateral injection of neither the orexin 1 and 2 receptor agonist orexin A (2 microg) nor the orexin 1 receptor antagonist SB 334867 (20 ng) into the nucleus accumbens Shell elicited turning behaviour. Unilateral injection of a mixture of dopamine D(1) (SKF 38393) and D2 (quinpirole) receptor agonists into the nucleus accumbens Shell has been found to elicit contraversive pivoting. Orexin A (1 and 2 microg) dose-dependently potentiated the contraversive pivoting induced by a mixture of SKF 38393 (1 microg) and quinpirole (10 microg) injected into the nucleus accumbens Shell whereas SB 334867 (10 and 20 ng) did not significantly affect the pivoting. The potentiating effect of orexin A (2 microg) on the dopaminergic pivoting was not significantly inhibited by SB 334867 (10 and 20 ng) injected into the nucleus accumbens Shell. The contraversive pivoting induced by a mixture of SKF 38393 (1 microg) and quinpirole (10 microg) injected into the nucleus accumbens Shell was also potentiated by the orexin 2 receptor agonist orexin B (0.5, 1 and 2 microg), which alone did not elicit turning behaviour. These results suggest that orexin 2 receptors in the nucleus accumbens Shell play a modulatory role in rat turning behaviour..  

Raising rats in isolation led to a significant decrease in CB1 receptor expression in the caudate putamen and the amygdala, a significant increase in FAAH expression in the caudate putamen and the nucleus accumbens core and Shell, and no significant change in D2 receptor expression in any region studied.  

Finally, the spontaneous recovery of cocaine-seeking was unaltered by manipulations of the dorsomedial prefrontal cortex (dPFC) and the nucleus accumbens Shell (Shell).  

This study investigated the effect of the AMPA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) microinjected into the core and Shell sub-regions of the accumbens nucleus (Acb), on the level of fear/anxiety and emotional learning, in female rats submitted to the elevated plus-maze (EPM), an animal model of anxiety. Bilateral microinjections of DNQX (330 and 660 ng) into the Acb Shell (AP, +1.08 to +2.16) induced an anxiolytic-like effect in relation to rats microinjected with vehicle, since there was an increased percentage of entries in the open arms of the maze. The 660 ng DNQX microinjection into the Acb Shell also increased the percentage of entries into the open arms in relation to 660 ng DNQX microinjection into the Acb core. Prior DNQX microinjections in both core and Shell sub-regions of the Acb failed to impair the emotional learning, since the animals exhibited an increase of the open arm avoidance on EPM Trial 2 in relation to EPM trial 1. The anxiolytic-like effect induced by DNQX suggests that the AMPA receptor in the Acb Shell, but not in the Acb core, may underlie anxiety regulation in the EPM..  

Continuous arterial spin labeling MRI measuring blood perfusion (as an indirect measure of activity) reveals that aripiprazole dose-dependently decreased brain activity in the entorhinal piriform cortex, perirhinal cortex, nucleus accumbens Shell, and basolateral amygdala.  

An impairment of stimulation-induced feeding manifesting as an elevation of the reaction threshold and a rightward, parallel shift of the stimulation frequency/reaction latency curve in the range of frequency which is sensitive to motivational aspects of food occurred after lesions localized mainly in the Acb Shell. The results obtained indicate that the Acb Shell connected with the limbic system but not the motor-related Acb core affects motivational aspects of feeding behaviour..  

The formation of monogamous pair bonds, by prairie voles, is facilitated by activation of dopamine (DA) D2-like, but not D1-like, receptors within the nucleus accumbens (NAcc) Shell. These manipulations were effective in the Shell, but not the core, of the NAcc. Together, these data demonstrate opposing regulation over pair bond formation by cAMP signaling within the NAcc Shell..  

In vivo microdialysis studies showed that in the Shell of the nucleus accumbens, dialysate DA was decreased following chronic lithium treatment and 3 days after withdrawal from lithium treatment.  

This effect is attenuated by inhibition of glutamate transmission in the ventral tegmental area and medial accumbens Shell, components of the mesolimbic dopamine system. When tested in the original drug self-administration context, systemic and medial or lateral accumbens Shell SCH 23390 injections attenuated context-induced reinstatement of heroin seeking, whereas accumbens core SCH 23390 injections were ineffective. In contrast, core but not lateral or medial Shell SCH 23390 injections attenuated discrete-cue-induced reinstatement in a nondrug context after extinction of lever presses without this cue. Results indicate that activation of medial and lateral accumbens Shell D1-family dopamine receptors mediate context-induced reinstatement of heroin seeking and provide the first demonstration for a role of lateral Shell dopamine in conditioned drug effects. Results also demonstrate novel dissociable roles of accumbens core and Shell in context- versus discrete-cue-induced reinstatement of heroin seeking..  

This pairing between context and drug increased Fos but not synaptophysin immunoreactivity in the nucleus accumbens core and Shell.  

The Shell division of the nucleus accumbens receives noradrenergic input from neurons in the nucleus of the solitary tract (NTS) that transmit information regarding fluctuations in peripheral hormonal and autonomic activity. Accumbens Shell neurons also receive converging inputs from limbic areas such as the hippocampus and amygdala that process newly acquired information. The beneficial effects on memory produced by emotional arousal and the corresponding activation of NTS neurons may be mediated through influences on neuronal activity in the accumbens Shell during memory encoding. To explore this putative relationship, Experiment 1 examined interactions between the NTS and the accumbens Shell in modulating memory for responses acquired after footshock training in a water-motivated inhibitory avoidance task. The enhanced retention produced by activating NTS neurons was attenuated by suppressing neuronal activity in the accumbens Shell with bupivacaine (0.25%/0.5 microl). Experiment 2 examined the direct involvement of accumbens Shell noradrenergic activation in the modulation of memory for psychologically arousing events such as a reduction in perceived reward value. Noradrenergic activation of the accumbens Shell with phenylephrine (1.0 microg/0.5 microl) produced an enhancement in memory for the frustrating experience relative to control injections as evidenced by runway performance on an extended seven-day retention test. These findings demonstrate a functional relationship between NTS neurons and the accumbens Shell in modulating memory following physiological arousal and identifies a role of norepinephrine in modulating synaptic activity in the accumbens Shell to facilitate this process..  

The results showed an activation of tyrosine hydroxylase gene expression in the ventral tegmental area and the substantia nigra, increased proenkephalin gene expression in the caudate-putamen, nucleus accumbens core and Shell, central and medial amygdala, ventromedial hypothalamic nucleus and the paraventricular hypothalamic nucleus.  

the nucleus accumbens (NAc) core and Shell as well as the ventral tegmental area (VTA) using in vivo microdialysis. STN-HFS leads to an increase in DA in the NAc, 2., these effects are more pronounced in the NAc Shell than in the NAc core, 3.  

In both species, withdrawal from repeated cocaine administration down-regulated Homer1b/c and Homer2a/b within the Shell, but not the core, of the nucleus accumbens (NAC), and the reduced Homer levels were accompanied by decreases in mGluR1a, NR2a and NR2b.  

The CB(1) receptor and proenkephalin gene expressions, and CB(1) receptor and mu-opioid (MO) receptor-mediated G-protein activation were found to be significantly lower in the caudate-putamen, nucleus accumbens core and Shell of FAAH -/- than +/+ mice.  

High-fat feeding also increased D2 binding in the nucleus accumbens Shell (36%).  

In parallel, the effects of asenapine on regional dopamine output using in vivo microdialysis in freely moving rats, dopamine output in the core and Shell subregions of nucleus accumbens (NAc) using in vivo voltammetry in anesthetized rats, and N-methyl-D: -aspartate (NMDA)-induced currents in pyramidal neurons of the medial prefrontal cortex (mPFC) using the electrophysiological technique intracellular recording in vitro were assessed. Low-dose asenapine (0.01 mg/kg, intravenous [ i.v.]) increased dopamine efflux preferentially in the Shell compared to the core of NAc, whereas at a higher dose (0.05 mg/kg, i.v.), the difference disappeared.  

Furthermore, sensitized D-rats showed a selective and significant increase in FosB expression in the nucleus accumbens (core and Shell), basolateral amygdala and medial prefrontal cortex, brain areas that are functionally related to the rewarding neural circuit.  

In the Shell of nucleus accumbens, dopamine extracellular levels were increased after administration of salvinorin A (40 microg/kg SC), reaching a maximum value of about 150%.  

In the nucleus accumbens, aripiprazole 30 mg/kg and clozapine increased Homer 1a and ania-3 transcripts in the Shell, whereas haloperidol induced expression of both isoforms in core and Shell.  

Consistent with Nrg1 HET mice exhibiting a schizophrenia-related phenotype, these mice expressed greater drug-free levels of c-Fos in two regions thought to be involved in schizophrenia, the Shell of the nucleus accumbens and the lateral septum.  

The weight gains were not the result of incidental damage to adjacent structures such as the stria terminalis or the Shell of the nucleus accumbens.  

It is suggested that differential distribution of the chemosensory units, demonstrated between subdivisions of the nucleus accumbens, has particular significance with respect to functional dichotomy of the Shell and core subregions..  

The goal of the present study was to analyse to what extent variables such as (1) injected volume, (2) nature of the solvent of drugs (saline versus distilled water) and (3) placement of an additional cannula to inject the solvent of the drugs at the opposite side of the brain, influenced the behavioural effects of the combined administration of the dopamine D(1) receptor agonist (+/-)-1-phenyl-2,3,4,5-tetrahydro-[ 1H]-3-benzazepine-7,8-diol (SKF 38393, 5.0 microg) and the dopamine D(2)/D(3) receptor agonist quinpirole (10.0 microg) into the Shell or core of the nucleus accumbens of freely moving rats. First, we found that increasing the injected volume from 0.2 microl to 0.5 microl significantly increased the amount of contralateral turning after injection of the drugs into the Shell and, especially, the core of rats equipped with one cannula. Second, replacing the solvent saline by distilled water resulted in a minor, but significant, decrease of the amount of contralateral turning elicited from either the Shell or the core of the nucleus accumbens of rats equipped with one cannula. Third, and most importantly, this study showed that the vehicle injection into the right core exerted a potentiating effect on the number of contralateral rotations elicited by injections of SKF 38393+quinpirole into the left core, whereas such a vehicle injection into the right Shell did not affect the number of contralateral rotations elicited by injections of SKF 38393+quinpirole into the left Shell.  

Cocaine-induced DA changes in the core and Shell of the nucleus accumbens in the same animals were also examined. There was, however, a significant decrease in the dopamine response to cocaine in the Shell of the nucleus accumbens.  

Lard-associated changes in c-Fos(+) cell numbers were observed in the nucleus of the tractus solitarius, lateral parabrachial nucleus, central nucleus of the amygdala, ventral tegmental area, nucleus accumbens Shell and the prefrontal cortex, and were associated with lower levels of triglycerides and free fatty acids.  

Apomorphine, however, reduced mating-induced Fos-immunoreactivity in the nucleus accumbens Shell and prevented its occurrence in its core area.  

Fos-ir activity was quantified in the paraventricular nucleus (PVN), subfornical organ (SFO), supraoptic nucleus (SON), nucleus accumbens (NAc) Shell and core, basolateral (BLA) and central amygdala (CeA), and medial prefrontal cortex (mPFC). Fos-ir activity was markedly enhanced in the SFO, BLA, and Shell of the NAc of 3F rats relative to 2V1F and 3V animals.  

Devalue rats showed greater FOS expression than Maintain rats in several brain regions implicated in devaluation task performance and the display of aversive responses, including the basolateral amygdala, orbitofrontal cortex, gustatory cortex (GC), and the posterior accumbens Shell (ACBs), whereas the opposite pattern was found in the anterior ACBs.  

Metabotropic glutamate (mGlu) 2/3 receptors regulate glutamate and dopamine release in the ventral tegmental area (VTA) and the nucleus accumbens (NAc) Shell, two brain areas critically involved in reward and motivational processes. Together, these findings indicate an important role for mGlu2/3 receptors in the posterior VTA and the NAc Shell in the mediation of the rewarding effects of nicotine and potentially in cue-induced nicotine-seeking behavior..  

This study investigated the effect of GABAA (muscimol, MUSC) and GABAB (baclofen, BACL) agonist receptors microinjected into medial accumbens Shell on feeding and the level of fear in free-feeding rats submitted to the elevated plus-maze (EPM), an animal model of anxiety. In addition to anxiolysis, the present study also showed that the microinjection of MUSC and BACL agonists into rostral sites of the medial Acb Shell (AP, +1.2 to +1.6) increased food intake significantly whereas drinking behaviour kept unchanged. The data indicated a putative role of GABA receptors (especially GABAB) in the medial Acb Shell for anxiety modulation in rats..  

The purpose of the present study was to investigate the effects of inactivating the dorsal striatum (DStr), nucleus accumbens (NAcc) core, or NAcc Shell on different types of responding, each maintained by drug-paired conditioned reinforcers. Inactivation of the DStr attenuated persistent responding for a cocaine-paired conditioned reinforcer, as well as its reacquisition after extinction of this response, while the only effect of inactivation of the NAcc Shell was to increase CS (cue)-induced reinstatement of the extinguished instrumental response that had previously delivered cocaine.  

This study examined the effects of simultaneous variations in motivational state (food deprivation) and reinforcer magnitude (food presentation) on c-Fos immunoreactivity in the pre- and infralimbic medial prefrontal cortex (mPFC), nucleus accumbens (NAcc) core and Shell, and dorsal striatum. In subjects 12 h deprived and allowed a small meal, c-Fos counts in prelimbic mPFC and NAcc core were positively correlated, as were those in infralimbic mPFC and NAcc Shell (r=0.83 and 0.76, respectively). The opposite was true of animals 36 h deprived, with prelimbic mPFC/NAcc core and infralimbic mPFC/NAcc Shell negatively correlated (r=-0.85 and -0.82, respectively). No differences between mean c-Fos counts were found, though prelimbic mPFC/NAcc core and mPFC/NAcc Shell were positively correlated in animals 36 h deprived (r=0.76 and 0.89, respectively).  

A single injection of PCP produced only small effects on stress-induced behavior and FLI: a drugxtime interaction on the number of cage crossings in the novel environment and a drugxcondition interaction on FLI in the Shell of the nucleus accumbens.  

A similar limbic selectivity of Lu 35-138 was indicated in voltammetric measure of dopamine output in the core and Shell subdivisions of the nucleus accumbens in rats.  

Furthermore, bilateral microinjections of SCH-23390 directly into the nucleus accumbens Shell fully blocked conditioned changes in NK activity. Collectively, these findings provide evidence that the nucleus accumbens Shell plays an important role in conditioned immunomodulation and further suggest that the conditioned and unconditioned immunomodulatory effects of opioids involve similar receptor mechanisms..  

METHODS: Microdialysis was applied to measure the dopamine overflow in the Shell region of NACC.  

Perfusion of NMDA (150 microM) into the Shell region of the accumbens produced a sustained increase (150-200%) in ACh release in prefrontal cortex.  

Such pro-erectile effect started 30 min after treatment and was abolished by the prior injection of d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin (1 microg), an oxytocin receptor antagonist injected into the same caudal ventral tegmental area or of haloperidol (1 microg), a dopamine receptor antagonist, injected either into the nucleus accumbens Shell (NAs) or into the paraventricular nucleus of the hypothalamus (PVN) ipsilateral to the injected ventral tegmental area. In the caudal ventral tegmental area oxytocin-containing axons/fibres (originating from the paraventricular nucleus) appeared to closely contact cell bodies of mesolimbic dopaminergic neurons retrogradely labelled with Fluorogold injected into the nucleus accumbens Shell, suggesting that oxytocin effects are mediated by the activation of mesolimbic dopaminergic neurons, followed in turn by that of incerto-hypothalamic dopaminergic neurons impinging on oxytocinergic neurons mediating penile erection.  

Although several biochemical and hormonal differences have been observed between Lewis and Fischer 344 strains, a systematic comparison of the effect of different drugs of abuse on dopamine (DA) transmission in the Shell and core of the nucleus accumbens of these strains is lacking. We therefore investigated, by means of dual probe microdialysis, the effect of different doses of morphine (1.0, 2.5, and 5.0 mg/kg), amphetamine (0.25, 0.5, and 1.0 mg/kg) and cocaine (5, 10, and 20 mg/kg) on DA transmission in the Shell and in the core of nucleus accumbens. In the NAc Shell, different effects were obtained depending on drug and dose: after 1.0 mg/kg of morphine no strain differences were observed, at 2.5 and 5.0 mg/kg Lewis rats showed greater increase in DA in the NAc Shell. Following amphetamine and cocaine challenge, Lewis rats showed greater DA increase in the Shell after 0.25 mg/kg of amphetamine and 20 mg/kg of cocaine.  

It has been reported that caffeine (1.5-30 mg/kg i.p.) as well as specific A1 (DPCPX, 8-cyclopentyl-1,3-dipropylxanthine) receptor antagonists fail to increase extracellular dopamine (DA) in the Shell of the nucleus accumbens (NAc). However, it has also been reported that caffeine (10 and 30 mg/kg i.p.) and the A1 antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT) increases NAc Shell DA. To clarify this issue rats were implanted with microdialysis probes at different sites in the NAc Shell, in the medial prefrontal cortex (PFCX, infralimbic cortex), and at the border between those areas. Irrespective of probe placement within the NAc Shell and of the use of different surgical anesthetics (chloral hydrate and ketamine), we failed to observe changes in dialysate DA after 10 and 30 mg/kg i.p. A significant increase of DA was obtained after caffeine when probes were located at the border between the NAc Shell and the PFCX (10 and 30 mg/kg) or in the PFCX (10 mg/kg). In view of this and of our previous report that caffeine increases dialysate DA in the medial PFCX, we conclude that the increase in dialysate DA by caffeine observed by others arises from the medial PFCX rather than from the NAc Shell as a result of placement of microdialysis probes at the border between the NAc Shell and the PFCX..  

In the present study we used the in vivo microdialysis technique to determine the actual extracellular levels of dopamine, its metabolites 3,4-dihydroxyphenyl acetaldehyde (DOPALD), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-HT and 5-hydroxyindolacetic acid (5-HIAA) in the Shell of nucleus accumbens of rat lines selectively bred as either high-ethanol (UChB) or low-ethanol (UChA) drinkers. Basal extracellular levels of dopamine, DOPALD, DOPAC and HVA were lower in the Shell of nucleus accumbens of ethanol-naïve UChB than in UChA rats.  

We studied the involvement of cocaine- and amphetamine-regulated transcript peptide (CART) in the central nucleus of amygdala (CeA), lateral bed nucleus of the stria terminalis (BNSTl) and nucleus accumbens Shell (AcbSh) in generation of ethanol withdrawal symptoms, with particular focus on anxiety-like behavior using a social interaction test.  

Except for strong hypothalamic expression, the CART transcript is predominately expressed in target regions of the mesocorticolimbic dopamine system, such as the nucleus accumbens Shell, amygdala complex, extended amygdala and orbitofrontal, enthorhinal and piriform cortices.  

RESULTS: After one injection, changes that were specific to U69593/QNP cotreatment were decreased D1R and D2R messenger RNA (mRNA) in the nucleus accumbens (Acb) Shell and increased DYN mRNA in the dorsal striatum (STR).  

However, NA lesions incompletely destroyed the NA Shell, the region most relevant for maternal behavior in rats, and should be investigated further.  

The present study investigated the in vivo effects of QNP and HAL on CRP40 protein levels within the core and Shell subcompartments of the NAcc. Results demonstrated that CRP40 protein was significantly expressed in the Shell relative to the core region of NAcc following chronic QNP (+16.28%+/-0.42%, P<0.05) and CRP40 protein was significantly expressed in the core vs. the Shell following chronic HAL (+36.02%+/-0.75%, P<0.05).  

Immediately before being returned to the self-administration chamber, we assessed the effects of gamma-aminobutyric acid agonist inhibition of midbrain DA regions (substantia nigra [ SN] and ventral tegmental area [ VTA]) and striatum (dorsolateral caudate-putamen, nucleus accumbens core, and nucleus accumbens Shell) on relapse to cocaine-seeking in the absence of reinforcement.  

Present experiments suggest that dopaminergic neurons localized in the posteromedial ventral tegmental area (VTA) and central linear nucleus raphe selectively project to the ventromedial striatum (medial olfactory tubercle and medial nucleus accumbens Shell), whereas the anteromedial VTA has few if any projections to the ventral striatum, and the lateral VTA largely projects to the ventrolateral striatum (accumbens core, lateral Shell and lateral tubercle). A review of the literature suggests that (1) the midbrain has corresponding zones for the accumbens core and medial Shell; (2) the striatal portion of the olfactory tubercle is a ventral extension of the nucleus accumbens Shell; and (3) a model of two dopamine projection systems from the ventral midbrain to the ventral striatum is useful for understanding reward function.  

In order to investigate the post-synaptic correlates of pre-synaptic changes in DA transmission and their relationship with MDMA enantiomers, we studied the effects of R,S(+/-)-MDMA, S(+)-MDMA, and R(-)-MDMA on extracellular DA and phosphorylated extracellular signal regulated kinase (pERK) in the NAc Shell and core. Male Sprague-Dawley rats, implanted with a catheter in the femoral vein and vertical concentric dialysis probes in the NAc Shell and core, were administered i.v. Intravenous R,S(+/-)-MDMA (0.64, 1, and 2 mg/kg) increased dialysate DA, preferentially in the Shell, in a dose-related manner.  

To explore the hypothesis that bupropion ameliorates nicotine withdrawal partly by a dopamine-dependent mechanism, we investigated the effects of chronic bupropion on potassium-stimulated dopamine overflow in the nucleus accumbens Shell in nicotine-withdrawing rats. Cessation of nicotine administration in non-bupropion-treated rats elevated reward thresholds reflecting a reward deficit, increased somatic signs and diminished potassium-evoked dopamine overflow in the nucleus accumbens Shell. In conclusion, the bupropion-induced increase in extracellular dopamine in the nucleus accumbens Shell may ameliorate the anhedonia associated with nicotine withdrawal, which in turn may facilitate smoking cessation..  

At the earliest withdrawal period, these behavioral changes were accompanied by elevations in FosB-like immunoreactive staining in the basolateral amygdala (BLA) and nucleus accumbens Shell (NAc-Sh) and core (NAc-C).  

One month after nicotine removal, the cannabinoid CB1 receptor antagonist, rimonabant, was injected bilaterally into the Shell of the nucleus accumbens (ShNAcc, 0.3, 3, or 30 ng/0.5 microl), the basolateral amygdala (BLA, 30 ng/0.5 microl), or the prelimbic cortex (PLCx, 30 ng/0.5 microl).  

A single subcutaneous (s.c.) injection of amphetamine (2.5 mg/kg) reduced the KOP receptor-mediated inhibition of glutamate release in the nucleus accumbens Shell, as a consequence of KOP receptor desensitization.  

BACKGROUND AND PURPOSE: Evidence indicates that the endocannabinoid, 2-arachidonoylglycerol (2-AG), increases food intake when injected into the nucleus accumbens Shell (NAcS), thereby potentially activating hypothalamic nuclei involved in food intake regulation.  

Only passively administered cocaine produced a decrease in dopamine D2 receptor levels in the anterior and central regions of caudate/putamen, and both the Shell and core of the nucleus accumbens, as measured by in vitro quantitative autoradiography.  

OBJECTIVES: This study investigated by repeated microdialysis sampling the inter- and intrasession changes in the responsiveness of the NAc Shell and core DA and the behavioral effects of active and passive heroin exposure in the intravenous self-administration/yoked paradigm. RESULTS: Dialysate DA increased preferentially in the Shell of master rats from the first session (+112%) and throughout the 4 weeks of self-administration (+130-140%). In yoked rats, a preferential but lesser increase in DA in the Shell was observed only on the first session (+60%), as the DA response in the NAc core increased progressively (+25-118%), so that within a week, the Shell/core ratio was reversed, and this pattern was maintained for the following 2 weeks. CONCLUSIONS: Chronic heroin self-administration increases extracellular DA preferentially in the NAc Shell.  

In rats, systemic administration of the selective alpha7 nicotinic acetylcholine receptor antagonist methyllycaconitine (MLA), but not the selective heteromeric non-alpha7 nicotinic acetylcholine receptor antagonist dihydrobetaerythroidine, (1) antagonized the discriminative effects of delta-9-tetrahydrocannabinol (THC), the main active ingredient in cannabis, (2) reduced intravenous self-administration of the synthetic cannabinoid CB1 receptor agonist WIN55,212-2 [ (R)-(+)-[ 2,3-dihydro-5-methyl-3[ (4-morpholinyl)methyl]pyrrolo[ 1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone, mesylate salt], and (3) decreased THC-induced dopamine elevations in the Shell of the nucleus accumbens.  

Previous studies have demonstrated that systemic or intra-accumbens Shell administration of an NMDA receptor antagonist reinstates cocaine-seeking behavior. However, it is unclear if antagonizing NMDA receptors in the nucleus accumbens core or Shell subregions will differentially affect cocaine reinstatement. To investigate this possibility, we microinjected the competitive NMDA receptor antagonist AP-5 (0, 3 or 30 microg) into either the nucleus accumbens core or Shell and assessed the reinstatement of cocaine-seeking behavior. When microinjected into the Shell, both doses of AP-5 produced reinstatement of cocaine seeking. In contrast, when administered into the core, only the highest dose of AP-5 reinstated cocaine-seeking behavior; moreover, the magnitude of this effect was substantially less than when AP-5 was administered into the Shell. This study provides evidence that pharmacological antagonism of NMDA receptors in the nucleus accumbens core or Shell promotes the reinstatement of cocaine seeking..  

In animals undergoing repeated immobilization stress and singly housed post-stress, we found a significant reversal in the direction of ENK-mRNA levels and DAT binding in the striatum, in addition to an increase in D2r-binding density in the Shell of the nucleus accumbens compared with single-stress-exposed rats.  

RESULTS: Immunohistochemical data show that the highest dose of ethanol (2 g/kg) rapidly increases p-cPKC immunoreactivity specifically in the nucleus accumbens (core and Shell), lateral septum, and hippocampus (CA3 and dentate gyrus).  

We have previously shown that increased expression of 5-HT(1B) receptors in nucleus accumbens (NAcc) Shell neurons sensitized rats to the locomotor-stimulating and rewarding properties of cocaine. Viral-mediated gene transfer techniques were used to overexpress 5-HT(1B) receptors in medial NAcc Shell medium spiny neurons projecting to the ventral tegmental area. Given this, we believe that increased 5-HT(1B) receptor activation in NAcc Shell projection neurons intensifies both the rewarding and negative properties of cocaine use..  

However, their subcellular localization in the nucleus accumbens core and Shell had not been compared to that of dorsal striatum. We showed that, among all presynaptic terminals forming asymmetric contact with dendritic processes, the percentage of D1R immunoreactive terminals was low in the dorsal striatum (8.2%), but reached in the nucleus accumbens core and Shell 25.5 and 29%, respectively.  

Previously, we reported that 17-beta estradiol reduced RGS9-2 mRNA expression in the Shell of the nucleus accumbens, but not the core. In situ hybridization histochemistry and Western blotting identified an inverse relationship between RGS9-2 protein expression in the nucleus accumbens Shell and the hormonal enhancement of amphetamine-induced place preference behavior. Moreover, treatment of ovariectomized female rats with the selective estrogen receptor-beta agonist, diarylpropionitrile (1 mg/kg), for 2 weeks also facilitated amphetamine-induced place preference behavior and selectively reduced nucleus accumbens Shell RGS9-2 protein expression.  

The apomorphine effect on prepulse inhibition is ascribed in part to altered synaptic transmission in the limbic-associated Shell and motor-associated core subregions of the nucleus accumbens (Acb). We used electron microscopic immunolabeling of dopamine D1 receptors (D1Rs) in the Acb Shell and core to test the hypothesis that region-specific redistribution of D1Rs is a short-term consequence of AS and/or apomorphine administration. In the Acb Shell, compared with the VEH+AS group, the APO+AS group had more spines containing D1R immunogold particles, and these particles were more prevalent on the plasma membranes. Small- and medium-sized dendrites also showed a higher plasmalemmal density of D1R in the Acb Shell of the APO+AS group compared with the APO group. These results suggest that alerting stimuli and apomorphine synergistically affect distributions of D1R in Acb Shell and core.  

METHODS: To determine which loci along the dopaminergic circuit are responsible for this behavior, 10-15 min before furosemide-treated adult male Sprague-Dawley rats were allowed 2-hour access to 2% salt solution (2-bottle choice), we pharmacologically blocked dopamine receptor subtype 1 (D1r) and subtype 2 (D2r) with SCH23390 or raclopride, respectively, and stimulated D1r with SKF81297 or D2r with quinpirole in the Shell of the Acb (AcbSh).  

Chronic administration of cocaine decreased N/OFQ in medial regions of the caudate putamen, the nucleus accumbens Shell, and the substantia nigra.  

METHODS: PPI was tested in male SD and LE rats after amphetamine (AMPH) was administered: 1) subcutaneously (sc), or intra-cerebrally (ic) into 2) the nucleus accumbens core (NACc; medial or lateral subregions) or the NAC Shell; 3) the anteromedial striatum (AMS) or 4) the posterior striatum (PS).  

The role of mesolimbic dopamine (DA) pathways in the development of EtOH reward was then examined by challenging EtOH-treated rats with bilateral intra-accumbens Shell applications of a DA receptor antagonist. When fluphenazine was administered into the nucleus accumbens Shell prior to the final test trial only (i.e., in already conditioned rats), intra-accumbens Shell DA receptor blockade was found to prevent the expression of CPPs produced by icv EtOH.  

The assumption of a novel high palatable food (a candied cherry) occurs concomitantly with an increase in the concentration of extra-cellular dopamine and its main metabolite 3,4-dihydroxy-phenylacetic acid (DOPAC) by about 45% in the dialysate obtained by intracerebral microdialysis from the Shell of the nucleus accumbens of male rats.  

Specifically, food cues increased cortical engagement of the striatum, and within the nucleus accumbens, shifted correlations away from the Shell towards the core.  

Both alpha7 nAChR agonists increased c-Fos dose-dependently in the prefrontal cortex and the Shell of nucleus accumbens, while leaving the core of nucleus accumbens and the dorsolateral striatum unaffected.  

DA variations were recorded in the dorsomedial Shell and core parts of the nucleus accumbens (Nacc) using in vivo voltammetry in freely-moving grown-up rats in a LI paradigm. In the third (test) session the following results were obtained in PE animals subjected to temporary inactivation of the ENT at PND8: (1) aversive behaviour was observed in TTX-PE conditioned animals; (2) DA variations in the dorsomedial Shell and core parts of the Nacc were similar in TTX-PE and non-pre-exposed conditioned rats.  

Cocaine (10 mg/kg i.p.) increased dopamine levels to 404 and 480% of baseline in the core and Shell of the NAc, respectively. Pretreatment with senktide at a dose of 0.2 mg/kg potentiated this effect to 666 (core) and 869% (Shell) of baseline, without having any effect on dopamine when given alone.  

IntraShell microinfusion of a D1, but not a D2 receptor antagonist, blocks ICSS. This work establishes a temporal link between anticipatory rises of dopamine and firing patterns in the NAc Shell during ICSS and suggests that they may play a similar role with natural rewards and during drug self-administration..  

Nicotine increased c-fos mRNA expression more robustly in the bed nucleus of the stria terminalis, nucleus accumbens Shell and ventral tegmental area in adolescent rats.  

Medium spiny neurons from nucleus accumbens (NAc) Shell were digitally reconstructed for morphometric analysis.  

To address this issue, we explored the effect of drug self-administration on interstitial eCB levels in the nucleus accumbens (NAc) Shell using in vivo microdialysis.  

Here we tested if anandamide microinjection into medial nucleus accumbens Shell enhances these affective reactions to sweet and bitter tastes in rats. Plume-based maps, integrated with behavioral data, identified the medial Shell of accumbens as the anatomical hotspot responsible for hedonic amplification. Anandamide produced especially intense hedonic enhancement in a roughly 1.6 mm3 'hedonic hotspot' in dorsal medial Shell, where anandamide also stimulated eating behavior. These results demonstrate that endocannabinoid signals within medial accumbens Shell specifically amplify the positive hedonic impact of a natural reward (though identification of the receptor specificity of this effect will require future studies).  

administrations of a relatively low dose of heroin (1 mg/kg, i.p.) induced psychomotor sensitization only when the treatment was administered in a relatively 'novel' environment (ie, a unique test environment distinct from the home cage) but not when the same treatment was administered in the home cage; (2) environmental novelty facilitated heroin-induced Fos expression in the caudate, particularly in its most caudal regions; (3) environmental context also modulated heroin-induced Fos expression in the nucleus accumbens and in the neocortex; (4) repeated exposures to heroin dramatically altered its effects on Fos expression in the caudate and in the neocortex; and (5) Fos protein levels in the postero-dorsal caudate, in the Shell of the nucleus accumbens, and in the barrel field cortex predicted most of the variance in heroin-induced activity scores, as shown by multiple regression analysis.  

Electrophysiological recordings were completed in rats (n = 14) trained to self-administer cocaine to determine whether activation of nucleus accumbens (Acb) neurons (core vs Shell) by cocaine-associated stimuli is enhanced after 1 month of cocaine abstinence. The cocaine stimulus significantly increased activation of Acb core (not Shell) neurons after 1 month of cocaine abstinence (compared with 1 d); this finding occurred regardless of contingency of cue presentation or cocaine availability.  

Changes in extracellular DA levels in the anterior NAcc Shell were measured via the no net flux (NNF) paradigm.  

At the 2 h time-point, c-Fos-like expression was shown to be significantly elevated (p<0.05) in the core and Shell of the nucleus accumbens, at both rostral and caudal levels, and in the lateral septum.  

Results revealed that glutamic acid decarboxylase (GAD(65)/GAD(67)) is higher abundant in the nucleus accumbens (NAc) than that in the caudate and medial prefrontal cortex (mPFC), while GABA(A) receptor alpha2 subunit level in the NAc Shell is less abundant than that in the NAc core, mPFC and caudate. Cocaine sensitization led to (1) a decrease in GAD(67) expression, an increase in total protein kinase C (PKC) zeta subtype and phosphorylated PKC zeta/lambda levels in the NAc core; (2) a decrease in GAD(67) and GABA(A) receptor alpha2 subunit expression, and an increase in phosphorylated PKC zeta/lambda levels in the NAc Shell; (3) an increase in GAD(67) expression in the caudate.  

Across different behavioural tasks, nucleus accumbens (n.acc) lesions have generated conflicting effects on locomotor activity and in particular, the relative roles of the n.acc Shell and core subfields in this have been controversial. Given the well-documented distinction between Shell and core, the present study sought to extend previous research by testing lesions selective to each n.acc subfield in the EPM. In contrast, Shell lesions consistently reduced locomotion and exploratory activity. In conclusion, locomotion and exploratory activity were clearly reduced by Shell but not core lesions, consistent with other evidence for the functional heterogeneity of n.acc Shell and core..  

The NAc Shell was separated into 5 zones of analysis previously defined by neurochemistry and connectivity. Repeated cocaine resulted in CREB phosphorylation in all analyzed subregions of the NAc excluding the most ventrolateral region of the Shell 2 weeks after cessation of repeated cocaine, but rats challenged after 2 drug-free days yielded a more localized activation of CREB in the 3 most dorsomedial zones of the Shell. The temporal and anatomical determinants of cocaine-induced CREB activity may indicate functional differences among NAc Shell subregions and suggest the involvement of CREB in early and late cocaine effects..  

Finally, evidence is reviewed that amino acid transmission specifically in the Acb Shell acts as a central 'circuit breaker' to flexibly enable or terminate the consummatory act, via descending connections to hypothalamic feeding control systems.  

Mu-opioid stimulation of cubic millimeter hedonic hotspots in either the nucleus accumbens Shell (NAc) or the ventral pallidum (VP) amplifies hedonic "liking" reactions to sweetness and appetitive "wanting" for food reward.  

These regions included (1) sites associated with thermoregulation such as the median preoptic nucleus, dorsomedial hypothalamus and raphe pallidus, (2) the supraoptic nucleus, a region important for osmoregulation and a key mediator of oxytocin and vasopressin release, (3) the medial and central nuclei of the amygdala, important in the regulation of social and emotional behaviors, and (4) the Shell of the nucleus accumbens and (anterior) ventral tegmental area, regions associated with the reinforcing effects of MDMA.  

Importantly, there was an increase in the percentage of cells colabeled with Fos and GluR1 in the anterior cingulate and nucleus accumbens Shell and cells colabeled with Fos and GluR4 in the infralimbic cortex, suggesting that within these regions, a greater, and perhaps even different, population of AMPA receptor subunit-expressing neurons is activated in rats engaged in cocaine-seeking behavior..  

Dose-dependent increases in extracellular levels of dopamine in selected brain areas, the nucleus accumbens (NAc) Shell and core, and the prefrontal cortex, were produced by cocaine but not by the preferential M1 antagonists telenzepine and trihexyphenidyl. When administered with cocaine, however, both M1 antagonists dose-dependently increased the effects of cocaine on dopamine in the NAc Shell, and these effects were selective in that they were not obtained in the NAc core or in the prefrontal cortex. The present results indicate that preferential antagonist effects at muscarinic M1 receptors do not uniformly alter all of the effects of cocaine, nor do they explain the differences in effects of cocaine and benztropine analogs, and that the alterations in dopamine levels in the NAc Shell do not predict the behavioral effects of the interactions with cocaine..  

In the dorsal, but not in the ventral, part of the Shell of the nucleus accumbens (NAc), blockade of A(1) receptors by local perfusion with the selective A(1) receptor antagonist 8-cyclopentyl-1,3-dimethyl-xanthine or by systemic administration of the non-selective adenosine antagonist caffeine induced a glutamate-dependent release of dopamine.  

Using a voltammetric sensor with high temporal and spatial resolution, we demonstrate differences in the temporal profile of dopamine concentration transients caused by acute doses of nicotine, ethanol, and cocaine in the nucleus accumbens Shell of freely moving rats.  


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