title: Role for ventral pallidal GABAergic mechanisms in the regulation of ethanol self-administration.
abstract: BACKGROUND
  The striatopallidal medium spiny neurons have been viewed as a final common path for drug reward, and the ventral pallidum (VP) as a convergent point for hedonic and motivational signaling. The medium spiny neurons are GABAergic, but they colocalize enkephalin.
  
  
  OBJECTIVE
  The present study investigated the role of the GABAergic mechanisms of the VP in ethanol consumption.
  
  
  METHODS
  The effects of bilateral microinjections of GABA(A) and GABA(B) receptor agonists and antagonists into the VP on voluntary ethanol consumption were monitored in alcohol-preferring Alko alcohol rats given 90 min limited access to ethanol in their home cages every other day. The influences of coadministration of GABA and opioid receptor modulators were also studied.
  
  
  RESULTS
  The GABA(A) receptor agonist muscimol (1-10 ng/site) decreased ethanol intake dose-dependently, while administration of the GABA(A) receptor antagonist bicuculline (10-100 ng) had an opposite effect. The GABA(B) receptor agonist baclofen (3-30 ng) also suppressed ethanol intake, but the GABA(B) receptor antagonist saclofen (0.3-3 μg) failed to modify it. Animals coadministered with bicuculline (30 ng) and baclofen (30 ng) consumed ethanol significantly less than those treated with bicuculline alone. Coadministration of the μ-receptor agonist D-Ala2,N-Me-Phe4,Glyol5-enkephalin (DAMGO, 0.1 μg) with bicuculline counteracted, whereas the μ-receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP, 1 μg) enhanced the bicuculline-induced increase of ethanol intake. When given alone, DAMGO decreased while CTOP increased ethanol intake.
  
  
  CONCLUSIONS
  The study provides evidence for the ventral pallidal GABAergic mechanisms participating in the regulation of ethanol consumption and supports earlier work suggesting a role for pallidal opioidergic transmission in ethanol reward.
authors.affiliation: Department of Alcohol, Drugs and Addiction, National Institute for Health and Welfare, POB 30, 00271 Helsinki, Finland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Kemppainen
authors.forename: Noora
authors.initials: N
authors.lastname: Raivio
authors.forename: Kalervo
authors.initials: K
authors.lastname: Kiianmaa
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism; D012646:Self Administration; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D011957:Receptors, Opioid; D000431:Ethanol; D005680:gamma-Aminobutyric Acid