title: Little evidence of a role for the α1GABAA subunit-containing receptor in a rhesus monkey model of alcohol drinking.
abstract: BACKGROUND
  Alcohol potentiates GABAergic neurotransmission via action at the GABAA receptor. α1 subunit-containing GABAA receptors have been implicated as mediators, in part, of the behavioral and abuse-related effects of alcohol in rodents.
  
  
  METHODS
  We systematically investigated the effects of 1 α1-preferring benzodiazepine agonist, zolpidem, and 2 antagonists, β-carboline-3-carboxylate-tert-butyl ester (βCCT) and 3-propoxy-β-carboline hydrochloride (3-PBC), on oral self-administration of alcohol (2% w/v) or sucrose solution and observable behavior in rhesus macaques. We compared these effects to those of the nonselective benzodiazepine agonist triazolam, antagonist flumazenil, and inverse agonist β-carboline carboxylate (βCCE).
  
  
  RESULTS
  Alcohol and sucrose solutions maintained reliable baseline drinking behavior across the study. The α1-preferring compounds did not affect intake, number of sipper extensions, or blood alcohol levels (BALs) at any of the doses tested. Zolpidem, βCCT, and 3-PBC increased latency to first sipper extension in animals self-administering alcohol, but not sucrose, solution. Triazolam exerted biphasic effects on alcohol-drinking behavior, increasing intake at low doses but decreasing BAL and increasing latency at higher doses. At doses higher than those effective in alcohol-drinking animals, triazolam increased sucrose intake and latency. Flumazenil nonsystematically increased number of extensions for alcohol but decreased BAL, with no effects on sucrose drinking. βCCE decreased sipper extensions for alcohol and increased latency for first sucrose sipper extension, but full dose-effect relationships could not be determined due to seizures at higher doses.
  
  
  CONCLUSIONS
  Alcohol-drinking animals appeared more sensitive to the effects of GABAergic compounds on drinking behavior. However, these results do not support a strong contribution of α1GABAA receptors to the reinforcing effects of alcohol in primates.
authors: New England Primate Research Center , Harvard Medical School, Southborough, Massachusetts.
authors: Eileen K
authors: EK
authors: Sawyer
authors: Casey
authors: C
authors: Moran
authors: Madelynn H
authors: MH
authors: Sirbu
authors: Melissa
authors: M
authors: Szafir
authors: Michael
authors: M
authors: Van Linn
authors: Ojas
authors: O
authors: Namjoshi
authors: V V N
authors: VV
authors: Phani Babu Tiruveedhula
authors: James M
authors: JM
authors: Cook
authors: Donna M
authors: DM
authors: Platt
mesh_terms: D000428:Alcohol Drinking / Q000517:prevention & control / Q000523:psychology*; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage; D058785:GABA-A Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D008253:Macaca mulatta; D008297:Male; D023421:Models, Animal; D021122:Protein Subunits / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D012646:Self Administration
chemical_list: D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; C546240:GABRA1 protein, human; D021122:Protein Subunits; D011963:Receptors, GABA-A; D000431:Ethanol
keywords: Alcohol; GABAA Receptors; Monkey; Pharmacotherapy; Self-Administration