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 D(2) 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 D(2) 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 microl/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 microM 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 microM 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 microM 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 D(2) autoreceptors in the NAc of P rats.
Engleman
Eric A
EA
Department of Psychology, Purdue School of Science, 402 N. Blackford Street, IUPUI, Indianapolis, IN 46202-3275, USA.
McBride
William J
WJ
Li
Ting-Kai
TK
Lumeng
Lawrence
L
Murphy
James M
JM
D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology*
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D000431:Ethanol; D013469:Sulpiride; D004298:Dopamine