title: Ethanol drinking experience attenuates (-)sulpiride-induced increases in extracellular dopamine levels in the nucleus accumbens of alcohol-preferring (P) rats.
abstract: 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.
authors.affiliation: Department of Psychology, Purdue School of Science, 402 N. Blackford Street, IUPUI, Indianapolis, IN 46202-3275, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engleman
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
authors.forename: Ting-Kai
authors.initials: TK
authors.lastname: Li
authors.forename: Lawrence
authors.initials: L
authors.lastname: Lumeng
authors.forename: James M
authors.initials: JM
authors.lastname: Murphy
mesh_terms: 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*
chemical_list: D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D000431:Ethanol; D013469:Sulpiride; D004298:Dopamine