title: Effects of the benzodiazepine GABAAα1-preferring antagonist 3-isopropoxy-β-carboline hydrochloride (3-ISOPBC) on alcohol seeking and self-administration in baboons.
abstract: The major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), modulates many of the behavioral effects of alcohol, including sedation, tolerance, and withdrawal. The α1 subunit of the benzodiazepine GABAAreceptor is the most widely expressed alpha subunit in the brain, and has been implicated in the reinforcing- and abuse-related effects of alcohol. The aim of the present study was to examine whether treatment with a benzodiazepine GABAAα1-preferring ligand, 3-isopropoxy-β-carboline hydrochloride (3-ISOPBC), selectively decreases alcohol seeking and consumption.
  
  
  
  Eight baboons self-administered alcohol (4% w/v; n=5; alcohol group) or a non-alcoholic beverage (n=3; control group) in Component 3 of a chained schedule of reinforcement. Responses in Component 2 provided indices of motivation to drink (seeking). Doses of 3-ISOPBC (5.0-30.0mg/kg) and vehicle were administered before drinking sessions under both acute and chronic (5day) conditions.
  
  
  
  Chronic, and not acute, administration of 3-ISOPBC significantly decreased self-administration responses, g/kg alcohol consumed, and the number of drinks in and duration of the first drinking bout in the alcohol group. In the control group, chronic administration of 3-ISOPBC did not significantly decrease any of these measures at any of the doses.
  
  
  
  The GABAAα1-preferring ligand 3-ISOPBC may have therapeutic potential in the treatment of alcohol use disorder due to its ability to selectively reduce alcohol use.
authors.affiliation: Johns Hopkins University School of Medicine, Division of Behavioral Biology, 5510 Nathan Shock Dr, Baltimore, MD 21224, USA.
authors.forename: August F
authors.initials: AF
authors.lastname: Holtyn
authors.affiliation: University of Wisconsin-Milwaukee, Department of Chemistry & Biochemistry, 3210 N Cramer St, Milwaukee, WI 53201, USA.
authors.forename: V V N Phani Babu
authors.initials: VV
authors.lastname: Tiruveedhula
authors.affiliation: University of Wisconsin-Milwaukee, Department of Chemistry & Biochemistry, 3210 N Cramer St, Milwaukee, WI 53201, USA.
authors.forename: Michael Rajesh
authors.initials: MR
authors.lastname: Stephen
authors.affiliation: University of Wisconsin-Milwaukee, Department of Chemistry & Biochemistry, 3210 N Cramer St, Milwaukee, WI 53201, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Cook
authors.affiliation: Johns Hopkins University School of Medicine, Division of Behavioral Biology, 5510 Nathan Shock Dr, Baltimore, MD 21224, USA. Electronic address: eweerts@jhmi.edu.
authors.forename: Elise M
authors.initials: EM
authors.lastname: Weerts
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy*; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage*; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009042:Motivation / Q000187:drug effects; D010215:Papio; D012054:Reinforcement, Psychology; D012646:Self Administration; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid
chemical_list: D058787:GABA-A Receptor Antagonists; D001569:Benzodiazepines; D000431:Ethanol; D005680:gamma-Aminobutyric Acid
keywords: 3-ISOPBC; 3-Isopropoxy-β-carboline hydrochloride; Alcohol; Baboon; Self-administration