Dopamine receptor regulation of ethanol intake and extracellular dopamine levels in the ventral pallidum of alcohol preferring (P) rats

Roberto I. Melendez, Zachary A. Rodd, William J. McBride, James M. Murphy

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Abstract

Sufficient evidence exists for the inclusion of the ventral pallidum (VP) into the category of a dopaminoceptive brain region. The effects of inhibiting dopamine D1- or D2-like receptors in the VP on (a) ethanol intake and (b) extracellular levels of dopamine, were investigated in the alcohol-preferring (P) rat. The D1-like antagonist, SCH-23390, and the D2-like antagonist, sulpiride (0.25-2 μg/0.5 μl) were bilaterally injected into the VP and ethanol (15%, v/v) intake was assessed in a 1 h limited access paradigm. The results indicate that microinjections of sulpiride significantly increased ethanol consumption (65% increase at the 2.0 μg dose). Whereas the D1 antagonists SCH-23390 tended to decrease ethanol intake, the effect was not statistically significant. In a separate group of rats, reverse microdialysis of sulpiride and SCH-23390 (10-200 μM) were conducted in the VP of P rats. Local perfusion of only the 200 μM sulpiride dose significantly increased the extracellular levels of dopamine (maximal increase: 250% of baseline). On the other hand, local perfusion of SCH-23390 (10-200 μM) dose dependently increased the extracellular levels of dopamine 180-640% of baseline. Overall, the results of this study suggest that (a) tonic activation of D2 postsynaptic receptors in VP imposes a limit on ethanol intake in the P rat; (b) there are few D2 autoreceptors functioning in the VP; (c) there is tonic D1-like receptor mediated inhibitory feedback regulation of VP-dopamine release.

Original languageEnglish (US)
Pages (from-to)293-301
Number of pages9
JournalDrug and Alcohol Dependence
Volume77
Issue number3
DOIs
StatePublished - Mar 7 2005

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Keywords

  • Alcohol preferring (P) rats
  • Dopamine
  • Ethanol
  • Microdialysis
  • Reinforcement
  • Ventral pallidum

ASJC Scopus subject areas

  • Medicine(all)
  • Behavioral Neuroscience
  • Toxicology
  • Health(social science)

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