Ethanol drinking experience attenuates (-)sulpiride-induced increases in extracellular dopamine levels in the nucleus accumbens of alcohol-preferring (P) rats

Background: The reinforcing properties of ethanol may be partly mediated through the mesolimbic dopamine (DA) system. This study examines the effects of local application of the DA D2 receptor antagonist (-)sulpiride (SUL) on ethanol drinking of alcohol-preferring (P) rats, and extracellular DA levels in the nucleus accumbens (NAc) of P rats that were either ethanol-naive or had been chronically drinking ethanol. Methods: Microdialysis was used to sample NAc DA levels, and reverse microdialysis was used to locally administer the D2 antagonist (-)sulpiride (SUL) into the NAc of adult female P rats that were either drinking ethanol (n= 17) or were ethanol-naive (n= 24). Stable intake of 15% (v/v) ethanol (≥0.75 g/kg) was established for the ethanol-drinking group in daily 1-hr access periods over a minimum of 4 weeks before surgery. Naive and ethanol-drinking rats were implanted with bilateral guide cannulae aimed 4 mm above the NAc shell. After recovery from surgery, microdialysis probes (active area = 2 mm) were inserted bilaterally into the NAc. Two days later, rats in the ethanol-drinking and naive groups were each divided into two groups; one group was bilaterally perfused (1.0 μl/min) with artificial cerebrospinal fluid (aCSF) and the other group was further divided into three subgroups that were perfused with aCSF + either 50, 100, or 200 μM SUL for 240 min. During the last 60 min of perfusion, the ethanol-drinking rats were given their daily 1-hr ethanol access period. Following ethanol access, the aCSF + SUL subgroups were then given aCSF only. The entire perfusion procedure was repeated 24 hr later, but the aCSF only and aCSF + SUL group treatment conditions were transposed. Results: In ethanol-drinking rats, 100 and 200 μM SUL increased extracellular NAc DA levels to approximately 200% of basal values, but did not significantly alter ethanol intake. In ethanol-naive P rats, 100 and 200 μM SUL increased extracellular NAc DA levels significantly more (450% of basal;p < 0.05) than in the ethanol-drinking group. Conclusions: The findings are consistent with the hypothesis that ethanol-drinking experience causes a desensitization or a down-regulation of D2 autoreceptors in the NAc of P rats.