title: Dopamine receptor regulation of ethanol intake and extracellular dopamine levels in the ventral pallidum of alcohol preferring (P) rats.
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 D(1)- or D(2)-like receptors in the VP on (a) ethanol intake and (b) extracellular levels of dopamine, were investigated in the alcohol-preferring (P) rat. The D(1)-like antagonist, SCH-23390, and the D(2)-like antagonist, sulpiride (0.25-2 microg/0.5 microl) 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 microg dose). Whereas the D(1) 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 microM) were conducted in the VP of P rats. Local perfusion of only the 200 microM 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 microM) dose dependently increased the extracellular levels of dopamine 180-640% of baseline. Overall, the results of this study suggest that (a) tonic activation of D(2) postsynaptic receptors in VP imposes a limit on ethanol intake in the P rat; (b) there are few D(2) autoreceptors functioning in the VP; (c) there is tonic D(1)-like receptor mediated inhibitory feedback regulation of VP-dopamine release.
authors.affiliation: Program in Psychobiology of Addictions, Department of Psychology, LD 124, Purdue School of Science, Indiana University-Purdue University at Indianapolis, IUPUI, 402 N. Blackford St., Indianapolis, IN 46202-3275, USA.
authors.forename: Roberto I
authors.initials: RI
authors.lastname: Melendez
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Rodd
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
authors.forename: James M
authors.initials: JM
authors.lastname: Murphy
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000502:physiology; D005246:Feedback / Q000502:physiology; D005260:Female; D005917:Globus Pallidus / Q000187:drug effects / Q000503:physiopathology*; D017551:Microdialysis; D008845:Microinjections; D009433:Neural Inhibition / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013469:Sulpiride; D004298:Dopamine