title: Effects of the benzodiazepine GABAA α1-preferring ligand, 3-propoxy-β-carboline hydrochloride (3-PBC), on alcohol seeking and self-administration in baboons.
abstract: BACKGROUND
  The various α subtypes of GABAA receptors have been strongly implicated in alcohol reinforcement and consumption.
  
  
  OBJECTIVE
  The effects of the GABAA α1-preferring ligand, 3-propoxy-β-carboline hydrochloride (3-PBC), on seeking and self-administration responses were evaluated in two groups of baboons trained under a 3-component chained schedule of reinforcement (CSR).
  
  
  METHODS
  Alcohol (4 % w/v; n = 5; alcohol group) or a preferred nonalcoholic beverage (n = 4; control group) was available for self-administration only in component 3 of the CSR. Responses in component 2 provided indices of motivation to drink (seeking). 3-PBC (1.0-30.0 mg/kg) and saline were administered before drinking sessions under both acute and 5-day dosing conditions.
  
  
  RESULTS
  Repeated, and not acute, doses of 3-PBC significantly decreased total self-administration responses (p < 0.05), volume consumed (p < 0.05), and gram per kilogram of alcohol (p < 0.05) in the alcohol group. In the control group, 5-day administration of 3-PBC significantly decreased total self-administration responses (p < 0.05) but produced nonsignificant decreases in volume consumed. Within-session pattern of drinking was characterized by a high level of drinking in the first 20 min of the session for both groups, which was significantly (p < 0.05) decreased by all doses of 3-PBC (1.0-18.0 mg/kg) only in the alcohol group. In contrast, the first drinking bout in the control group was only reduced at the highest doses of 3-PBC (10.0 and 18.0 mg/kg).
  
  
  CONCLUSIONS
  The results support the involvement of the GABAA α1 subtype receptor in alcohol reinforcement and consumption.
authors.affiliation: Division of Behavioral Biology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224, USA.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Kaminski
authors.forename: Michael L
authors.initials: ML
authors.lastname: Van Linn
authors.forename: James M
authors.initials: JM
authors.lastname: Cook
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Yin
authors.forename: Elise M
authors.initials: EM
authors.lastname: Weerts
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy* / Q000523:psychology; D001569:Benzodiazepines; D002243:Carbolines / Q000008:administration & dosage*; D000431:Ethanol / Q000008:administration & dosage* / Q000009:adverse effects; D008024:Ligands; D008297:Male; D010215:Papio; D011963:Receptors, GABA-A / Q000378:metabolism*; D012055:Reinforcement Schedule; D012646:Self Administration; D016896:Treatment Outcome
chemical_list: C454686:3-propoxy-beta-carboline; D002243:Carbolines; D008024:Ligands; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D000431:Ethanol