Acoustic startle and fear-potentiated startle in alcohol-preferring (P) and -nonpreferring (NP) lines of rats

The objective of the present study was to determine whether alcohol-preferring P and -nonpreferring NP rats differ in their acoustic startle response and in fear-potentiated startle. In Experiment 1, male P and NP rats were tested on the startle response to acoustic stimuli ranging from 90-115 dB. Experiments 2 and 3 examined fear-potentiated startle and extinction of the response. In Experiment 2, rats received two light foot shock training sessions separated by 3-4 h. Testing consisted of ten acoustic startle (115 dB) and fear-potentiated startle (light preceding the acoustic startle) presentations administered every 24 h for 9 consecutive days. To test potentiated startle learning under reduced training conditions, a single training session was administered in Experiment 3, and a single within-session extinction test of 50 startle and 50 potentiated startle trials occurred the following day. Results of Experiment 1 indicated that P and NP rats did not differ in startle at any of the acoustic intensities tested. Following fear-potentiated startle conditioning in Experiment 2, however, both acoustic startle and potentiated startle responding were consistently greater in P than NP rats over most of the first 6 test days with P rats having approximately a 100% greater acoustic startle and 50-100% greater potentiated startle response. Moreover, following a single training session in Experiment 3, only P rats showed significant fear-conditioned startle. Additionally, P rats exhibited a 50-100% elevated acoustic startle response over that observed in NP rats. Taken together, the data indicate that, although experimentally naive male P and NP rats show similar acoustic startle responses, P rats become more responsive to both startle-alone and potentiated startle stimuli following fear conditioning. The change in general startle reactivity of the P rat following aversive conditioning, along with facilitated light foot shock learning, suggests that stress exposure may be an important variable in examining associations between anxiety and alcohol drinking behavior.     

Contents of monoamines in forebrain regions of alcohol-preferring (P) and -nonpreferring (NP) lines of rats

The contents of monoamine neurotransmitters and metabolites were assayed in the frontal cortex, nucleus accumbens and anterior striatum of rats from the selectively bred alcohol-preferring P and nonpreferring NP lines. Lower levels of serotonin (20-30%) in all three brain regions of P as compared with NP rats lends support to the hypothesis that a decreased metabolic activity and/or innervation by serotonin neurons is associated with the abnormally high volitional intake of ethanol. Of additional interest, however, were the approximately 25% lower contents of dopamine and its major metabolites in the nucleus accumbens of the P rats. This observation may indicate that P rats have a specific deficiency in the dopaminergic projections from the ventral tegmental area to the nucleus accumbens and, since the accumbens is an important structure in brain reward circuitry, it might also be an important determinant of the excessive volitional intake of alcohol by P rats.     

Differential effects of ethanol in the nucleus accumbens shell of alcohol-preferring (P), alcohol-non-preferring (NP) and Wistar rats: A proteomics study

The objective of this study was to determine the effects of ethanol injections on protein expression in the nucleus accumbens shell (ACB-sh) of alcohol-preferring (P), alcohol-non-preferring (NP) and Wistar (W) rats. Rats were injected for 5 consecutive days with either saline or 1 g/kg ethanol; 24 h after the last injection, rats were killed and brains obtained. Micro-punch samples of the ACB-sh were homogenized; extracted proteins were subjected to trypsin digestion and analyzed with a liquid chromatography-mass spectrometer procedure. Ethanol changed expression levels (1.15-fold or higher) of 128 proteins in NP rats, 22 proteins in P, and 28 proteins in W rats. Few of the changes observed with ethanol treatment for NP rats were observed for P and W rats. Many of the changes occurred in calcium-calmodulin signaling systems, G-protein signaling systems, synaptic structure and histones. Approximately half the changes observed in the ACB-sh of P rats were also observed for W rats. Overall, the results indicate a unique response to ethanol of the ACB-sh of NP rats compared to P and W rats; this unique response may reflect changes in neuronal function in the ACB-sh that could contribute to the low alcohol drinking behavior of the NP line.     

Ethanol anticipation enhances dopamine efflux in the nucleus accumbens of alcohol-preferring (P) but not Wistar rats

It has been argued that the anticipation of ethanol consumption can activate reinforcement substrates involved in alcohol-seeking behavior. To test this hypothesis nucleus accumbens (NAc) dopamine (DA) efflux was monitored in alcohol-preferring (P) and Wistar rats. Rats from each line were divided into two groups: one trained to self-administer 0.05% saccharin and the other trained to self-administer 10% (w/v) ethanol. On the test day dopamine efflux was monitored in all animals during saccharin self-administration. In ethanol-expecting P rats, self-administration of saccharin produced a significant elevation in extracellular DA (150% of baseline within the first 15-20min). In contrast, a significant increase in extracellular DA was only observed during the final 30min of the test session in ethanol-expecting Wistar rats self-administering saccharin. The self-administration of saccharin in animals expecting the sweetener failed to elevate extracellular DA in both strains. Overall, these results suggest that the mere expectation of ethanol availability enhances the efflux of DA in the NAc of the P, but not the Wistar rat, which may play a role in the initiation or maintenance of ethanol seeking behavior in the P line.     

Effects of Ro 15-4513, fluoxetine and desipramine on the intake of ethanol, water and food by the alcohol-preferring (P) and -nonpreferring (NP) lines of rats

The effects of the IP administration of RO 15-4513 (1,2 and 4 mg/kg), fluoxetine (5 and 10 mg/kg) and desipramine (5 and 10 mg/kg) on the intake of 10% ethanol, H₂O and food were determined in the selectively bred alcohol-preferring (P) and -nonpreferring (NP) lines of rats with daily access to fluids being limited to single 2-hour sessions. The imidazobenzodiazepine Ro 15-4513 (a partial inverse benzodiazepine agonist) significantly reduced the intake of 10% ethanol by the P rats to 50–60% of control levels in the first 30 minutes without altering food or H₂O intake. The attenuating actions of 2 mg/kg Ro 15-4513 on ethanol intake could be completely blocked by the central benzodiazepine receptor antagonist Ro 15-1788 (10 mg/kg). Ro 15-1788, by itself, produced no effects on alcohol and H₂O consumption. The 5 mg/kg dose of fluoxetine significantly reduced 10% ethanol intake by the P rats to 20% of control values without altering either H₂O or food consumption. The 10 mg/kg dose of fluoxetine further reduced ethanol intake by the P rats, but this dose also reduced daily food intake to approximately 70% of normal. Desipramine at both doses significantly (p<0.05) reduced both ethanol and food uptake by the P rats and had a tendency to reduce H₂O consumption as well. In general, the three drugs had effects in the NP rats similar to those observed for the P group, although the effects on 10% ethanol intake were difficult to compare because of the low, variable intake of alcohol by the NP group. The data are consistent with the involvement of serotonin and the GABA-benzodiazepine receptor complex in alcohol drinking behavior.     

A comparison of the reinforcing efficacy of alcohol in alcohol-preferring (P) and alcohol-nonpreferring (NP) rats

A key feature of the selective breeding program that produced alcohol-preferring (P) and alcohol-nonpreferring (NP) rats is that the alcohol was mixed with water. However, humans typically drink sweetened or palatably flavored alcohol. The experiments in this study tested whether the differences in P and NP rats generalize to sweetened alcohol. In Experiment 1, P rats drank more alcohol than NP rats when the vehicle was water, but NP rats drank about as much alcohol as P rats (1.1 to 1.3 g/kg/30 min) when the vehicle was a saccharin solution. Experiment 2 tested whether P rats were more susceptible to the rewarding properties of sweetened alcohol than were NP rats. The criterion for reward strength was the degree to which alcohol-reinforced lever pressing persisted, despite increases in the schedule requirements for the alcohol reward. In baseline, lever presses were reinforced with sweetened alcohol and an isocaloric Polycose solution according to two, concurrent, variable-interval 5-s schedules. In subsequent conditions, the interval schedule for alcohol was increased, and then, after a return to baseline, the interval schedule for Polycose was increased. By the criterion of resistance to change, alcohol was a stronger reinforcer than was Polycose, and alcohol was a stronger reinforcer in NP rats than in P rats.     

CB1 receptors regulate alcohol-seeking behavior and alcohol self-administration of alcohol-preferring (P) rats

Rationale

The endogenous cannabinoid (CB) system mediates a number of behaviors associated with drug-seeking and drug self-administration. In this study the effects of CB1 receptor manipulations on operant ethanol (EtOH) responding during EtOH-seeking, EtOH-relapse as well as on-going EtOH self-administration were determined.

Methods

Alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15% EtOH (v/v) and water on a concurrent fixed-ratio 5-fixed-ratio 1 (FR5-FR1) schedule of reinforcement in daily 1-h sessions. After 10 weeks, rats underwent 7 extinction sessions, followed by 2 weeks in their home cages without access to EtOH or operant chambers. Rats were then returned to the operant chambers for testing of EtOH-seeking behavior (no EtOH present) for 4 sessions. After a week in their home cages following the EtOH-seeking test, rats were returned to the operant chambers with access to EtOH and water (relapse). Rats were then maintained in the operant chambers for daily 1-h sessions with access to 15% EtOH and water for several weeks.

Results

The CB1 receptor antagonist (SR141716A), at doses of 1 and 2 mg/kg, i.p. reduced EtOH-seeking and transiently reduced EtOH self-administration during relapse and maintenance. Conversely, treatment with the CB1 receptor agonist CP 55, 940, at doses of 1 and 10 μg/kg i.p., increased EtOH-seeking and EtOH self-administration during relapse.

Conclusions

The results of this study demonstrate that activation of CB1 receptors are involved in regulating EtOH-seeking as well as the reinforcing effects of EtOH under relapse and on-going self-administration conditions.     

Microinjections of phencyclidine (PCP) and related drugs into nucleus accumbens shell potentiate medial forebrain bundle brain stimulation reward

 Microinjections of phencyclidine (PCP) into the ventro-medial portion of nucleus accumbens in rats potentiated the rewarding impact of lateral hypothalamic brain stimulation. Similar effects were found with nomifensine, which shares with PCP the ability to block dopamine uptake and thus elevate synaptic dopamine levels but does not share with PCP the ability to block NMDA receptors. Similar effects were also seen with dizocilpine (MK-801) and [3-((±)2-carboxypiperazin-4-yl)propyl-1-phosphonate] (CPP), which share with PCP the ability to block NMDA receptors but not to block dopamine uptake. Thus PCP’s properties as a dopamine uptake inhibitor and as an NMDA receptor antagonist each appear capable of producing reward-related actions in this brain region. The common denominator of these two PCP actions is decreased output of medium spiny neurons; these neurons are tonically activated by a glutamate projection from prefrontal cortex (PCP blocks this source of activation) and are tonically inhibited by a dopaminergic projection from the ventral tegmental area (PCP augments this inhibition). Received: 10 April 1996 / Final version: 5 August 1996     

Role of nucleus accumbens dopamine D1 and D2 receptors in instrumental and Pavlovian paradigms of conditioned reward

RATIONALE: This study investigated the role of nucleus accumbens dopamine D1 and D2 receptors in two different paradigms of conditioned reward. OBJECTIVE: We addressed the question whether accumbal dopamine is important for the motor or for the motivational components of reward. METHODS: We compared the effects of intra-accumbal infusion of the dopamine D1 receptor antagonist SCH23390 (0.3, 1.0, 3.0 microg) and the D2 receptor antagonist sulpiride (0.3, 1.0, 3.0 microg) on conditioned lever pressing for food, with the effects on the inhibition of the startle response by a conditioned reward signal. RESULTS: Both the D1 and the D2 antagonist dose-dependently attenuated conditioned lever pressing for reward under a fixed-ratio of responding and increased the consumption of freely available lab chow. However, the preference for freely available pellets, and the attenuation of the startle response in the presence of a conditioned stimulus predicting reward were not impaired by blockade of accumbal dopamine receptors. CONCLUSIONS: Our data support the idea that dopamine in the nucleus accumbens is necessary for instrumental response selection in the context of reward rather than for the mere motor performance of behavior or for the evaluation of the hedonic properties of rewarding stimuli.     

Ethanol induces stronger dopamine release in nucleus accumbens (shell) of alcohol-preferring (bibulous) than in alcohol-avoiding (abstainer) rats

Several studies on the differences between ethanol-preferring versus non-preferring rat lines suggest an innate deficit in the mesolimbic dopaminergic system as an underlying factor for ethanol volition. Rats would try to overcome such deficit by engaging in a drug-seeking behaviour, when available, to drink an ethanol solution over water. 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. It is reported that under basal conditions extracellular dopamine levels are lower in the bibulous than in the abstainer rats, while ethanol induced a 2-fold greater increase of dopamine release in bibulous than in abstainer rats. The greater effect of ethanol in bibulous rats was not associated to differences in blood ethanol levels, since the concentration and elimination of ethanol were virtually identical in both rat lines, indicating that bibulous rats are more sensitive to the stimulation of dopamine release by ethanol than abstainer rats. No differences were observed in 5-hydroxytryptamine or metabolites measured simultaneously under basal or ethanol-stimulating conditions in bibulous and abstainer rats. Overall, the present results suggest that a low dopaminergic tone and a strong mesolimbic dopamine response to ethanol are concerted neurochemical features associated to an ethanol-seeking behaviour in rats.     

Regional CNS densities of serotonin 1A and dopamine D2 receptors in periadolescent alcohol-preferring P and alcohol-nonpreferring NP rat pups

The objective of the present study was to use quantitative autoradiography to determine binding densities of serotonin(1A) (5-HT(1A)) and dopamine (DA) D(2) receptors in alcohol-naive periadolescent P and NP rat pups. P (n=8) and NP (n=7) rat pups, 25 days of age, from different litters were used. Coronal brain sections were incubated with 2 nM [3H]8-OH-DPAT or 20 nM [3H]sulpiride for 5-HT(1A) or D(2) binding, respectively. Approximately 15-40% higher densities of [3H]8-OH-DPAT binding were observed in the anterior cortical regions of the periadolescent P rat compared with NP rat pups. Similar differences were also observed in posterior cortical regions with P rats having 25-40% higher [3H]8-OH-DPAT binding than NP rats. [3H]8-OH-DPAT binding was approximately 10-20% higher in posterior hippocampal regions of the P rat pups compared with the NP line. [3H]sulpiride binding was significantly different only in the ventral tegmental area (VTA), where binding was approximately 20% lower in the periadolescent P rats compared with the NP rat pups. Overall, these results are very similar to findings observed in adult alcohol-naive P and NP rats, and suggest that the innate differences in the neural systems implicated in high alcohol drinking behaviors may already be established in the periadolescent animal.     

Psychomotor-activating effects mediated by dopamine D(2) and D(3) receptors in the nucleus accumbens

The contribution made by specific dopamine receptor subtypes to the induction of motor behaviors has not been firmly established. Here, we first characterized the behavioral effects induced by a D(2)-class receptor agonist, bromocriptine, following injections into the nucleus accumbens (Acb). Bromocriptine showed an atypical D(2)-class receptor agonist profile, having no observable effect on a range of motor behaviors. However, when coadministered with the D(1)-class receptor agonist SKF 38393, bromocriptine showed a typical D(2)-class receptor agonist profile, enhancing locomotor activity and suppressing spontaneous yawning. We then administered the dopamine receptor antagonists L-741626 and nafadotride, which possess relative selectivity for D(2) and D(3) receptors, respectively, prior to injections of dopamine agonists into the Acb. Nafadotride significantly reduced the locomotor-enhancing effects elicited by the coadministration of SKF 38393 and the D(2)-class receptor agonist (+)-PD 128907 into the Acb, and also attenuated the effects induced by the combination of SKF 38393 and bromocriptine, although not significantly so. L-741626 mildly attenuated the locomotor effects elicited by both drug combinations. Taken together, these results suggest that both D(2) and D(3) receptors in the Acb contribute to the expression of heightened psychomotor activation.     

Contralateral turning elicited by unilateral stimulation of dopamine D2 and D1 receptors in the nucleus accumbens of rats is due to stimulation of these receptors in the shell,but not the core,of this nucleus

The goal of this study was to determine whether dopamine D₂ and/or D₁ receptors in the shell and the core of the nucleus accumbens of rats have a differential role in turning behaviour. Unilateral injection of a mixture of the dopamine D₂ receptor agonist quinpirole (10 µg) and the dopamine D₁ receptor agonist 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7, 8-diol (SKF 38393, 5 µg) into the shell of the nucleus accumbens produced contralateral turning, when doses which per se were ineffective were injected. This effect was far greater than that found after similar injections into the core of the nucleus accumbens. The effect elicited from the shell was significantly attenuated by prior administration of either the dopamine D₂ receptor antagonistl-sulpiride (25 ng/0.5 µl) or the dopamine D₁ receptor antagonist (8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol (SCH 23390, 0.5 µg/0.5 µl) into the same region. These data together with the fact thatl-sulpiride is known to be a valid tool to differentiate the involvement of distinct regions within the shell underlie the conclusion that dopamine D₂ and D₁ receptors in the shell, but not the core, of the nucleus accumbens play a critical role in the contralateral turning induced by unilateral injection of dopamine receptor agonists into this nucleus. The results are discussed in view of the known output pathways of the shell.     

Blockade of GABA(A) receptors within the extended amygdala attenuates D(2) regulation of alcohol-motivated behaviors in the ventral tegmental area of alcohol-preferring (P) rats

The dopamine (DA) mesolimbic pathway, which originates from DA cell bodies within the ventral tegmental area (VTA), has been shown by various studies to play a role in the mediation of various drugs of abuse including alcohol (EtOH). It has been suggested that the VTA's control of EtOH reward is mediated in part by the D2 receptors within the VTA. These receptors may be under the regulation of reciprocal GABAergic inputs from forebrain components of the mesolimbic path such as the nucleus accumbens (NAcc), a classic EtOH reward substrate, and the bed nucleus of the stria terminalis, a substrate recently implicated in EtOH reinforcement, forming a self-regulating feedback loop. To test this hypothesis, D2 regulation of EtOH self-administration (SA) was evaluated by the microinfusion of the D2 antagonist eticlopride into the VTA of P rats, which produced profound reductions in EtOH SA in the highest (20.0 and 40.0 μg) doses tested in both BST/VTA and NAcc/VTA implanted P rats. To determine the role of GABA in the mediation of EtOH SA, a 32.0 ng dose the non-selective GABA antagonist SR 95531 was microinfused into the BST producing no effect on responding for EtOH and into the NAcc which lead to a reduction in EtOH responding. Finally, the hypothesis that GABA innervation of the VTA from the mesolimbic forebrain may influence EtOH SA was examined by the simultaneous infusion of eticlopride (40.0 μg) into the VTA and SR 95531 (32.0 ng) into either the BST or NAcc. This combination infusion completely attenuated the reduction in EtOH SA observed with the 40.0 μg dose of eticlopride alone in both groups of animals. These results suggest that while the D2 receptors within the VTA regulate EtOH-motivated behaviors, this is modulated by GABAergic input from the mesolimbic forebrain, specifically from the BST and NAcc.     

Locomotor activity stimulation in rats produced by dopamine in the nucleus accumbens: potentiation by caffeine.

The increased motor activity of reserpine-nialamide pretreated rats given dopamine into the nucleus accumbens was potentiated in a dose-dependent manner by systemically administered caffeine. Similarly, the increase in motor activity seen when the endogenous dopamine was released by intraperitoneally administered amphetamine was potentiated by systemically given caffeine. These effects might be due to an increase in the dopamine-induced accumulation of cyclic AMP in the nucleus accumbens after inhibition of the phosphodiesterase by caffeine.     

The stimulation of cholecystokinin receptors in the rostral nucleus accumbens significantly antagonizes the EEG and behavioural effects induced by phencyclidine in rats

The influence of cholecystokinin (CCK), bilaterally injected into the rostral nucleus accumbens, on the EEG and behavioural effects induced by phencyclidine (PCP) has been studied in rats. CCK (10 ng) significantly inhibited PCP-induced EEG effects (increase of spectral power with respect to pre-drug tracing; increase of relative power distribution in the slowest frequency bands), and behavioural effects (circling and ataxia). The inhibitory effects of CCK were completely antagonized by 1 ng PD 135–158, a selective CCK_B receptor antagonist, but not by lorglumide (1 µg), a selective CCK_A receptor antagonist. Since the effects induced by PCP in rodents have been proposed to be an experimental correlate of the psychotic symptoms it induces in humans, these results indicate that CCK may act as a neuroleptic. They also suggest that CCK_B receptors located in the rostral nucleus accumbens may be involved in the neuroleptic-like activity of CCK.     

Stimulation of adenosine receptors in the nucleus accumbens reverses the expression of cocaine sensitization and cross-sensitization to dopamine D(2) receptors in rats

Adenosine receptors co-localize with dopamine receptors on medium spiny nucleus accumbens (NAc) neurons where they antagonize dopamine receptor activity. It remains unclear whether adenosine receptor stimulation in the NAc restores cocaine-induced enhancements in dopamine receptor sensitivity. The goal of these studies was to determine whether stimulating A₁ or A_2A receptors in the NAc reduces the expression of cocaine sensitization. Rats were sensitized with 7 daily treatments of cocaine (15 mg/kg, i.p.). Following one-week withdrawal, the effects of intra-NAc microinjections of the adenosine kinase inhibitor (ABT-702), the adenosine deaminase inhibitor (deoxycoformycin; DCF), the specific A₁ receptor agonist (CPA) and the specific A_2A receptor agonist (CGS 21680) were tested on the behavioral expression of cocaine sensitization. The results indicate that intra-NAc pretreatment of ABT-702 and DCF dose-dependently blocked the expression of cocaine sensitization while having no effects on acute cocaine sensitivity, suggesting that upregulation of endogenous adenosine in the accumbens is sufficient to non-selectively stimulate adenosine receptors and reverse the expression of cocaine sensitization. Intra-NAc treatment of CPA significantly inhibited the expression of cocaine sensitization, which was reversed by both A₁ and A_2A receptor antagonism. Intra-NAc treatment of CGS 21680 also significantly inhibited the expression of cocaine sensitization, which was selectively reversed by A_2A, but not A₁, receptor antagonism. Finally, CGS 21680 also inhibited the expression of quinpirole cross-sensitization. Together, these findings suggest that adenosine receptor stimulation in the NAc is sufficient to reverse the behavioral expression of cocaine sensitization and that A_2A receptors blunt cocaine-induced sensitization of postsynaptic D₂ receptors.     

Effects of accumbens DALA microinjections on brain stimulation reward and behavioral activation in intact and 6-OHDA treated rats

The effects of bilateral nucleus accumbens microinjections ofd-ala-met-enkephalinamide (DALA) were assessed in behavioral activation and lateral hypothalamic self-stimulation (LHSS) rate-frequency curve-shift paradigms in normal and accumbens 6-OHDA (4.0 µg) treated rats. Microinjections of DALA (2.5 µg/µl) in the behavioral activation paradigm had little effect on normal activity; however, DALA administered to 6-OHDA treated rats produced a significant overall increase in locomotion. The 6-OHDA DALA-induced locomotion effect peaked at 2 weeks after 6-OHDA treatment and then returned to baseline levels by week 5 posttreatment. Using LHSS, DALA tested over a range of doses (2.5, 5, 10, 20 µg/µl) displayed a weak biphasic reward effect only at the highest dose, which was characterized by an initial suppression followed by an elevation. DALA significantly depressed initial operant motor/performance in LHSS in a dose dependent fashion. Micro-injections of the normally ineffective low dose of DALA (2.5 µg/µl) following accumbens 6-OHDA treatment produced a significant LHSS reward decrease 2 weeks posttreatment, while LHSS motor/performance was relatively unaffected. Results are discussed in terms of opiate-dopamine and limbic-motor interactions.     

Role of dopamine D-1 and D-2 receptors in the regulation of neurotensin systems of the neostriatum and the nucleus accumbens

Activation of dopamine D-1 receptors with multiple administrations of SKF 38393 significantly increased the level of neurotensin-like immunoreactivity in the striatum and the nucleus accumbens. However, a similar treatment with the D-2 receptor-selective agonist, LY 171555, decreased the same in both structures; when the two drugs were administered concureently, their individual effects were blocked. These results suggest that dopamine D-1 and D-2 receptors antagonistically regulate neurotensin systems of the striatum and nucleus accumbens. On the other hand, blockade of D-2 receptors (with sulpiride) elevated, while D-1 receptors blockade (with SCH 23390) caused no change in the level of neurotensin in both these structures. Dopamine D-1 receptors did not appear to contribute to the sulpiride-mediated effect as concurrent administration of SCH 23390 did not alter the response.     

Suppression of feeding-evoked dopamine release in the rat nucleus accumbens by the blockade of P(2) purinoceptors

In order to investigate whether endogenous adenosine 5'-triphosphate (ATP) is involved in the regulation of feeding, the influence of the P(2) receptor antagonist pyridoxalphospate-6-azophenyl-2', 4'-disulphonic acid (PPADS) infused into the rat nucleus accumbens on 18-h food-deprived feeding was tested. PPADS suppressed the feeding-induced dopamine release and reduced the amount of food consumed as well as the time of feeding. These results indicate that activation of P(2) purinoceptors by endogenous ATP facilitates feeding behaviour and contributes to the feeding-associated dopamine release.