D1 Receptors In Nucleus Accumbens Research Articles

Nucleus accumbens D1-receptors regulate and focus transitions to reward-seeking action

It is well established that dopamine transmission is integral in mediating the influence of reward expectations on reward-seeking actions. However, the precise causal role of dopamine transmission in moment-to-moment reward-motivated behavioral control remains contentious, particularly in contexts where it is necessary to refrain from responding to achieve a beneficial outcome. To examine this, we manipulated dopamine transmission pharmacologically as rats performed a Go/No-Go task that required them to either make or withhold action to gain either a small or large reward. D1R Stimulation potentiated cue-driven action initiation, including fast impulsive actions on No-Go trials. By contrast, D1R blockade primarily disrupted the successful completion of Go trial sequences. Surprisingly, while after global D1R blockade this was characterized by a general retardation of reward-seeking actions, nucleus accumbens core (NAcC) D1R blockade had no effect on the speed of action initiation or impulsive actions. Instead, fine-grained analyses showed that this manipulation decreased the precision of animals’ goal-directed actions, even though they usually still followed the appropriate response sequence. Strikingly, such “unfocused” responding could also be observed off-drug, particularly when only a small reward was on offer. These findings suggest that the balance of activity at NAcC D1Rs plays a key role in enabling the rapid activation of a focused, reward-seeking state to enable animals to efficiently and accurately achieve their goal.

Metal brain bioaccumulation and neurobehavioral effects on the wild rodent Liomys irroratus inhabiting mine tailing areas.

Ecotoxicological studies are necessary in order to evaluate the effects of environmental exposure of chemicals on wild animals and their ecological consequences. Particularly, neurobehavioral effects of heavy metal elements on wild rodents have been scarcely investigated. In the present study, we analyzed the effect of metal bioaccumulation (Pb, As, Mg, Ni, and Zn) in the brain and in the liver on exploratory activity, learning, memory, and on some dopaminergic markers in the wild rodent Liomys irroratus living inside mine tailings, at Huautla, Morelos, Mexico. We found higher Pb concentration but lower Zn in striatum, nucleus accumbens, midbrain, and hippocampus in exposed animals in comparison to rodents from the reference site. Exposed rodents exhibited anxious behavior evaluated in the open field, while no alterations in learning were found. However, they displayed slight changes in the memory test in comparison to reference group. The neurochemical evaluation showed higher levels of dopamine and 5-hydroxyindolacetic acid in midbrain, while lower levels of metabolites dihydroxyphenyl acetic acid and homovanillic acid in striatum of exposed rodents. In addition, mRNA expression levels of dopaminergic D2 receptors in nucleus accumbens were lower in animals from the mining zone than in animals from the reference zone. This is the first study that shows that chronic environmental exposure to metals results in behavioral and neurochemical alterations in the wild rodent L. irroratus, a fact that may comprise the survival of the individuals resulting in long-term effects at the population level. Finally, we suggest the use of L. irroratus as a sentinel species for environmental biomonitoring of mining sites.

Neuromedin U induces self-grooming in socially-stimulated mice

Emerging evidence suggest that appetite-regulating peptides modulate social behaviors. We here investigate whether the anorexigenic peptide neuromedin U (NMU) modulates sexual behavior in male mice. However, instead of modulating sexual behaviors, NMU administered into the third ventricle increased self-grooming behavior. In addition, NMU-treatment increased self-grooming behavior when exposed to other mice or olfactory social-cues, but not when exposed to non-social environments. As the neuropeptide oxytocin is released during social investigation and exogenous oxytocin induces self-grooming, its role in NMU-induced self-grooming behavior was investigated. In line with our hypothesis, the oxytocin receptor antagonist inhibited NMU-induced self-grooming behavior in mice exposed to olfactory social-cues. Moreover, dopamine in the mesocorticolimbic system is known to be a key regulator of self-grooming behavior. In line with this, we proved that infusion of NMU into nucleus accumbens increased self-grooming behavior in mice confronted with an olfactory social-cue and that this behavior was inhibited by antagonism of dopamine D2, but not D1/D5, receptors. Moreover repeated NMU treatment enhanced ex vivo dopamine levels and decreased the expression of dopamine D2 receptors in nucleus accumbens in socially housed mice. On the other hand, the olfactory stimuli-dependent NMU-induced self-grooming was not affected by a corticotrophin-releasing hormone antagonist, and NMU-treatment did not influence repetitive behaviors in the marble burying test. In conclusion, our results suggest that NMU treatment and, social cues - potentially triggering oxytocin release - together induce excessive grooming behavior in male mice. The mesolimbic dopamine system, including accumbal dopamine D2 receptors, was identified as a crucial downstream mechanism.

Long-term effects of iloperidone on cerebral dopamine receptor subtypes.

The atypical antipsychotic drug iloperidone has high affinity for a wide range of neurotransmitter receptors, including dopaminergic (DA), serotonergic, and adrenergic receptors. We examined the long-term effects of multiple doses of iloperidone on DA D1 , D2 , D3 , and D4 receptor subtypes. Sprague-Dawley adult rats (n=8/group) received daily intraperitoneal injections of iloperiodone (0.5, 1, or 5mg/kg) or vehicle for 4 weeks. Receptor autoradiography quantified the levels of DA receptors in medial prefrontal cortex (MPC), dorsolateral frontal cortex (DFC), caudate putamen (CPu), nucleus accumbens (NAc), and hippocampus (HIP). Four weeks of iloperidone treatment at 5mg/kg significantly increased D1 receptors in NAc (36%) and CPu (38%). Iloperidone (1.5 and 5mg/kg) dose-dependently increased D2 receptors in MPC (37 and 47%) and HIP (32 and 40%). Only the high dose of iloperidone (5mg/kg) increased D2 receptors in NAc (39%) and CPu (38%). Repeated treatment with iloperidone (1.5 and 5mg/kg) increased D4 receptors in the NAc (39 and 78%), CPu (42 and 83%) and HIP (54 and 72%). The three doses of iloperidone failed to alter D3 receptors in the brain regions examined in this study. These results suggest that iloperidone exerts region- and dose-specific effects on forebrain DA receptor subtypes, which may contribute to its therapeutic benefits in improving the positive and negative symptoms of schizophrenia with minimal extrapyramidal side effects.

Impact of Early Consumption of High-Fat Diet on the Mesolimbic Dopaminergic System.

Increasing evidence suggest that consumption of high-fat diet (HFD) can impact the maturation of brain circuits, such as during adolescence, which could account for behavioral alterations associated with obesity. In the present study, we used behavioral sensitization to amphetamine to investigate the effect of periadolescent HFD exposure (pHFD) in rats on the functionality of the dopamine (DA) system, a central actor in food reward processing. pHFD does not affect responding to an acute injection, however, a single exposure to amphetamine is sufficient to induce locomotor sensitization in pHFD rats. This is paralleled by rapid neurobiological adaptations within the DA system. In pHFD-exposed animals, a single amphetamine exposure induces an increase in bursting activity of DA cells in the ventral tegmental area (VTA) as well as higher DA release and greater expression of (tyrosine hydroxylase, TH) in the nucleus accumbens (NAc). Post-synaptically, pHFD animals display an increase in NAc D2 receptors and c-Fos expression after amphetamine injection. These findings highlight the vulnerability of DA system to the consumption of HFD during adolescence that may support deficits in reward-related processes observed in obesity.

Dopamine release in nucleus accumbens during rewarded task switching measured by [11C]raclopride

Reward and motivation have positive influences on cognitive-control processes in numerous settings. Models of reward implicate corticostriatal loops and the dopamine (DA) system, with special emphasis on D2 receptors in nucleus accumbens (NAcc). In this study, 11 right-handed males (35–40 years) were scanned with positron emission tomography (PET) in a single [11C]raclopride dynamic scan during rewarded and non-rewarded task switching. Rewarded task switching (relative to baseline task switching) decreased [11C]raclopride binding in NAcc. Decreasing NAcc [11C]raclopride binding was strongly associated with task reaction time measures that reflect individual differences in effort and control strategies. Voxelwise analyses additionally revealed reward-related DA release in anterodorsal caudate, a region previously associated with task-switching. These PET findings provide evidence for striatal DA release during motivated cognitive control, and further suggest that NAcc DA release predicts the task reaction time benefits of reward incentives.

Dopamine preferentially inhibits NMDA receptor-mediated EPSCs by acting on presynaptic D1 receptors in nucleus accumbens during postnatal development.

Nucleus accumbens (nAcb), a major site of action of drugs of abuse and dopamine (DA) signalling in MSNs (medium spiny neurons), is critically involved in mediating behavioural responses of drug addiction. Most studies have evaluated the effects of DA on MSN firing properties but thus far, the effects of DA on a cellular circuit involving glutamatergic afferents to the nAcb have remained rather elusive. In this study we attempted to characterize the effects of dopamine (DA) on evoked glutamatergic excitatory postsynaptic currents (EPSCs) in nAcb medium spiny (MS) neurons in 1 to 21 day-old rat pups. The EPSCs evoked by local nAcb stimuli displayed both AMPA/KA and NMDA receptor-mediated components. The addition of DA to the superfusing medium produced a marked decrease of both components of the EPSCs that did not change during the postnatal period studied. Pharmacologically isolated AMPA/KA receptor-mediated response was inhibited on average by 40% whereas the isolated NMDA receptor-mediated EPSC was decreased by 90%. The effect of DA on evoked EPSCs were mimicked by the D1-like receptor agonist SKF 38393 and antagonized by the D1-like receptor antagonist SCH 23390 whereas D2-like receptor agonist or antagonist respectively failed to mimic or to block the action of DA. DA did not change the membrane input conductance of MS neurons or the characteristics of EPSCs produced by the local administration of glutamate in the presence of tetrodotoxin. In contrast, DA altered the paired-pulse ratio of evoked EPSCs. The present results show that the activation D1-like dopaminergic receptors modulate glutamatergic neurotransmission by preferentially inhibiting NMDA receptor-mediated EPSC through presynaptic mechanisms.

Self-administration of propofol is mediated by dopamine D1 receptors in nucleus accumbens in rats

As a widely used intravenous short-acting anesthetic, propofol is recently indicated by clinical and animal studies for its abuse potential, but the mechanism underlying propofol abuse is largely unknown. This study examined the contribution of dopamine receptor subtype (D1 and D2 receptors) and neuroanatomical locus (i.e. nuclear accumbens) in the maintenance of propofol self-administration in rats. After the acquisition and maintenance of self-administration of propofol (1.7mg/kg/infusion) under a fixed ratio (FR1) schedule of reinforcement over 14days, rats were treated by either intraperitoneal injection or intra-nucleus accumbens (NAc) injection of D1 receptor antagonist (SCH23390) or D2 receptor antagonists (spiperone and eticlopride) 10min prior to the subsequent propofol self-administration. We demonstrated (i) systemic administration of SCH23390 (10, 30, 100μg/kg, i.p.) dose-dependently decreased the rate of propofol-maintained self-administration, suggesting a critical role of the D1 receptor in mediating propofol self-administration; (ii) the blockade of the propofol self-administration by SCH23390 was specific since spiperone and eticlopride did not affect propofol self-administration and SCH23390 at these doses did not affect food-maintained responding under an FR5 schedule; (iii) intra-accumbenal injection of SCH23390 (2.5μg/site) but not eticopride (3.0μg/site) attenuated the propofol self-administration, localizing nuclear accumbal D1 receptors as a critical locus in the reinforcement of propofol. Together, these findings provide the first direct evidence that D1 receptors in nuclear accumbens play an important role in the maintenance of propofol self-administration.

Gentiopicroside Attenuates Morphine Rewarding Effect through Downregulation of GluN2B Receptors in Nucleus Accumbens

Gentiopicroside (Gent) is one of the secoiridoid compound isolated from Gentiana lutea. This compound exhibits analgesic activities and inhibits the expression of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the anterior cingulate cortex in mice. Nucleus accumbens (NAc) is a forebrain structure known for its role in drug addiction. However, little is known about the role of Gent on morphine dependence and synaptic transmission changes in the NAc. Conditioned place preference (CPP) test and behavioral sensitization of locomotor activity were used to investigate drug-seeking related behaviors. Brain slices containing NAc were prepared, and whole-cell patch-clamp recordings were performed to record the excitatory postsynaptic currents (EPSCs). Expression of proteins was detected by Western blot analysis. Systemic administration of Gent attenuated the CPP effect induced by morphine, but had no effect on morphine-induced behavioral sensitization. Gent significantly reversed overexpression of GluN2B-containing NMDA receptors and dopamine D2 receptors in NAc during the first week of morphine withdrawal. However, the compound did not affect the overexpression of GluN2A-containing NMDA receptors, GluA1, and dopamine D1 receptors. Lastly, Gent significantly reduced NMDA receptors-mediated EPSCs in the NAc. Our study provides strong evidence that Gent inhibits morphine dependence through downregulation of GluN2B-containing NMDA receptors in the NAc.

Roles of hippocampal NMDA receptors and nucleus accumbens D1 receptors in the amphetamine-produced conditioned place preference in rats

There are glutamatergic projections from the hippocampus to the nucleus accumbens (NAc), which regulate DA transmission in this structure. To be precise, the ventral hippocampal (VH) glutamatergic neurons project to the nucleus accumbens shell region (NAcSh), whereas the dorsal hippocampus (DH) sends glutamatergic projections to the nucleus accumbens core region (NAcC). This study investigates the roles of hippocampal N-methyl- d-aspartate (NMDA) glutamate receptors and NAc type 1 dopamine receptor (D1) in amphetamine-produced conditioned place preference (AMPH-CPP) in rats. Our earlier reports showed that AMPH-CPP results in the enhancement of hippocampal CaMKII activity and it can be impaired by NMDA antagonist (AP5). In this study AMPH-CPP did not alter the NAc CaMKII activity, although AMPH-CPP was impaired by a blockade of D1 receptors (SCH23390) during conditioning. Moreover, inactivation of hippocampal area (dorsal hippocampus or ventral hippocampus) impaired AMPH-CPP, but its effect was diminished by the activation of D1 receptors in accumbal region (NAc core or NAc shell). By inactivating both DH and NAc core resulted in the disruption of rat’s CPP expression. However, the impaired CPP expression was recovered during the next testing session, suggesting the disruption of CPP expression was a short term effect. Moreover, the disruption of CPP expression was not exhibited if NAc core was not inactivated. Interestingly, the rats that received activation in VH but an inactivation in NAc shell before testing show impaired CPP expression compared to those received inactivation in both VH and NAc shell. DH activation plus an inactivation in NAc core before testing show a significantly higher rate of the weakening of AMPH-CPP expression. Similarly, an activation of VH plus an inactivation of NAc shell before testing also show a statistically significant lower CPP score on tests 3 and 4. These results, taken together, indicate that NMDA receptor activation in DH and VH have different enhancing effects on the AMPH-CPP as their innervations onto the different NAc regions are essential for AMPH-CPP establishment. If the deterioration of AMPH-CPP expression (or extinction process) resembles the formation of new learning, then this active process might have been facilitated by the hippocampal NMDA receptor activations during testing.

P.2.d.011 Genes expression and protein levels in rat brain, dependent on time passage after administration of antidepressant dugs

The antipsychotic effects of neuroleptics are believed to be mediated via dopamine D2 receptor blockade; however, the anatomical and pharmacological targets of these drugs remain somewhat controversial. The purpose of this study was to examine the effects of chronic clozapine (CLZ) and haloperidol (HAL) treatments on the densities of DA D1 and D2 receptors. Adult male Sprague–Dawley rats (300–350 g) were treated for 21 days with either HAL (1 mg/kg/day, i.p.), CLZ (20 mg/kg/day, i.p.) or saline. Three days after ending the treatments, the brains were removed and used for biochemical assays of tissue DA and metabolites as well as for receptor studies. DA D1 and D2 receptors were labelled with [3H]SCH23390 and [3H]raclopride, respectively, and measured in the neostriatum by binding studies, and in autoradiograms of forebrain sections by quantitative densitometry. The autoradiographic measurements revealed significant increases in the densities of D2 receptors in nucleus accumbens, in the medio-ventral, latero-dorsal and latero-ventral quadrants of the rostral neostriatum, in caudal neostriatum and in globus pallidus of both HAL- (28–44%) and CLZ-treated (15–85%) animals. The HAL-induced up-regulation of D2 receptors in rostral and caudal neostriatum was homogenous, but CLZ produced a more uneven increase, with the highest absolute densities measured in latero-dorsal neostriatum, as well as with changes in the medio-dorsal rostral neostriatum. For D1 receptors, only CLZ and not HAL, produced significant increases in five regions, namely nucleus accumbens (43%), latero-dorsal rostral neostriatum (16%), caudal neostriatum (30%), globus pallidus (67%) and substantia nigra (12%). The observation that CLZ, contrary to HAL, also has an effect on D1 receptor densities may explain the greater therapeutic and selective efficacy with fewer side-effects of this agent, in comparison to other neuroleptics.

P.4.b.007 Spontaneous alternation behaviour as an animal model of OCD; the role of dopamine D2 receptors in nucleus accumbens

Many factors contribute to sleep disturbance among young adults. Social media (SM) use is increasing rapidly, and little is known regarding its association with sleep disturbance.In 2014 we assessed a nationally representative sample of 1788 U.S. young adults ages 19–32. SM volume and frequency were assessed by self-reported minutes per day spent on SM (volume) and visits per week (frequency) using items adapted from the Pew Internet Research Questionnaire. We assessed sleep disturbance using the brief Patient-Reported Outcomes Measurement Information System (PROMIS®) sleep disturbance measure. Analyses performed in Pittsburgh utilized chi-square tests and ordered logistic regression using sample weights in order to estimate effects for the total U.S. population.In models that adjusted for all sociodemographic covariates, participants with higher SM use volume and frequency had significantly greater odds of having sleep disturbance. For example, compared with those in the lowest quartile of SM use per day, those in the highest quartile had an AOR of 1.95 (95% CI = 1.37–2.79) for sleep disturbance. Similarly, compared with those in the lowest quartile of SM use frequency per week, those in the highest quartile had an AOR of 2.92 (95% CI = 1.97–4.32) for sleep disturbance. All associations demonstrated a significant linear trend.The strong association between SM use and sleep disturbance has important clinical implications for the health and well-being of young adults. Future work should aim to assess directionality and to better understand the influence of contextual factors associated with SM use.

Involvement of dopamine D1 and D2 receptors in the rat nucleus accumbens in immunostimulation

Analysis of the nature of changes in the immune response in operated Wistar rats showed that electrolytic lesioning of the nucleus accumbens, the site of the greatest density of dopamine D1 and D2 receptors, led to suppression of the immune response in animals immunized with sheep erythrocytes. Administration of SKF 38393 (20 mg/kg) and quinpirol (1 mg/kg), selective agonists of dopamine D1 and D2 receptors respectively, to sham-operated rats induced significant increases in immune responses. However, no immunostimulation was seen on administration of the selective dopamine D2 agonist quinpirol to animals with lesions to the nucleus accumbens as compared with controls. At the same time, treatment of animals with nucleus accumbens lesions using the dopamine D1 receptor agonist SKF 38393 had no effect on the immune response as compared with that in sham-operated animals given the D1 receptor agonist. These data provide evidence that dopamine D2 receptors in the nucleus accumbens have a role in the mechanisms of immunostimulation, though D2 receptors in other brain structures may also make some contribution to this process; D1 receptors in the nucleus accumbens make no significant contribution to controlling the immune response.

Enhanced effect of dopaminergic stimulation on prepulse inhibition in mice deficient in the alpha subunit of Gz

G(z) is a member of the G(i) G protein family associated with dopamine D2-like receptors; however, its functions remain relatively unknown. The aim of the present study was to investigate prepulse inhibition (PPI) of acoustic startle, locomotor hyperactivity and dopamine D2 receptor binding in mice deficient in the alpha subunit of G(z). We used automated startle boxes to assess startle and PPI after treatment with saline, amphetamine, apomorphine or MK-801. We used photocell cages to quantitate locomotor activity after amphetamine treatment. Dopamine D2 receptor density was determined by autoradiography. Startle responses and baseline PPI were not different between the Galpha(z) knockout mice and wild-type controls (average PPI 46+/-4 vs 49+/-3%, respectively). Amphetamine treatment caused a marked disruption of PPI in Galpha(z) knockouts (average PPI 22+/-2%), but less so in controls (average PPI 42+/-3%). Similar genotype-dependent responses were seen after apomorphine treatment (average PPI 23+/-3% vs 40+/-3%), but not after MK-801 treatment (average PPI 29+/-5 vs 33+/-2%). Amphetamine-induced locomotor hyperactivity was greater in Galpha(z) knockouts than in controls. There was no difference in the density of dopamine D2 receptors in nucleus accumbens. Mice deficient in the alpha subunit of G(z) show enhanced sensitivity to the disruption of PPI and locomotor hyperactivity caused by dopaminergic stimulation. These results suggest a possible role for G(z) in neuropsychiatric illnesses with presumed dopaminergic hyperactivity, such as schizophrenia.

NMDA and dopamine interactions in the nucleus accumbens modulate cortical acetylcholine release

The nucleus accumbens (NAC) plays a key role in directing appropriate motor output following the presentation of behaviorally relevant stimuli. As such, we postulate that accumbens efferents also participate in the modulation of neuronal circuits regulating attentional processes directed toward the identification and selection of these stimuli. In this study, N-methyl-d-aspartate (NMDA) and D1 ligands were perfused into the shell region of the NAC of awake rats. Cortical cholinergic transmission, a mediator of attentional processes, was measured via microdialysis probes inserted into the prefrontal cortex (PFC). NMDA perfusions (150 or 250 microm) into NAC resulted in significant increases in acetylcholine (ACh) efflux in PFC (150-200% above baseline levels). Co-administration of the D1 antagonist SCH-23390 (150 microm) markedly attenuated (by approx. 70%) ACh efflux following perfusions of 150 microm NMDA but not following 250 microm NMDA, suggesting that D1 receptor activity contributes to the ability of the lower but not the higher concentration of NMDA to increase cortical ACh release. Collectively, these data reveal a positive modulation of NMDA receptors by D1 receptors in NAC that is expressed trans-synaptically at the level of cortical transmission. This modulation may underlie the coordinated linking of attentional processes and motor output following exposure to salient and behaviorally relevant stimuli.

The effects of D1 or D2 dopamine receptor antagonism in the medial preoptic area, ventral pallidum, or nucleus accumbens on the maternal retrieval response and other aspects of maternal behavior in rats.

The medial preoptic area (MPOA), ventral pallidum (VP), and nucleus accumbens (NA) receive dopaminergic afferents and are involved in maternal behavior. Experiments investigated whether dopamine (DA) receptor antagonism in NA disrupts maternal behavior, determined the type of DA receptor involved, and investigated the involvement of drug spread to VP or MPOA. Injection of SCH 23390 (D1 DA receptor antagonist) into NA of postpartum rats disrupted retrieving at dosage levels that were ineffective when injected into MPOA or VP. Motor impairment was not the cause of the deficit. Injection of eticlopride (D2 DA receptor antagonist) into NA or VP was without effect. Results emphasize the importance of DA action on D1 receptors in NA for retrieval behavior.

Sex differences in dopamine receptor overproduction and elimination.

Density of dopamine D1 and D2 family receptors was assessed using autoradiography in male and female rats from 25 to 120 days of age, focusing on transitions through puberty into full adulthood. Males had greater overproduction (approximately 4.6-fold) and elimination of striatal D1 and D2 receptors than females, though their adult densities were very similar. Males had more extensive overproduction of D1 receptors in nucleus accumbens and sustained a greater density into adulthood (57.8 +/- 21.2%). These results have implications for understanding gender differences in the prevalence of clinical disorders associated with dopamine.

Modifications of head turning and circling movement following sulpiride microinjections into nucleus accumbens in the rat

The aim of this study was to determine whether a relationship exists between nucleus accumbens D2 receptors, circling behavior, and its first stage, the head turning. Rats were unilaterally lesioned in the substantia nigra with 6-hydroxydopamine and afterward treated with d-amphetamine IP Following bilateral intraaccumbens microinjections (1, 5, 10 μg/0.5 μl) of sulpiride, a D2 receptor antagonist. Computer-assisted video analysis allowed the study of some parameters (number of turns, type of turn, head turning duration, degree and speed) characterizing rotatory activity. Sulpiride microinfusion resulted in a dose-dependent decrease of the number of turns and head rotation speed and in a dose-dependent increase of head-turning duration. Two turn types were observed in relation to the animal's position: a large head-to-tail position with a short-diameter turn type following sulpiride microinjection, and a close head-to-tail position in relation to a wide diameter turn type in the control condition (saline). The results show a relationship between head turning parameters, circling behavior, and D2 receptors in nucleus accumbens, which may be also involved in the regulation of some mechanisms related to sensory-motor integration in the rat.

RAPID COMMUNICATION: ALCOHOL-PREFERRING RATS HAVE FEWER DOPAMINE D<sub>2</sub> RECEPTORS IN THE LIMBIC SYSTEM

Dopamine D2 receptors in nucleus accumbens, olfactory tubercle and caudate nucleus of Sardinian ethanol-preferring (SP), and non-preferring (SNP) rats were compared by using [3H]YM-09151-2 binding. SP rats exhibited, in each area, lower density of D2 receptors than SNP and unselected Wistar (UW) rats. The results suggest that reduction in D2 receptors in SP rats may be relevant to their innate preference for alcohol.