title: Contribution of alpha1 subunit-containing gamma-aminobutyric acidA (GABAA) receptors to motor-impairing effects of benzodiazepines in squirrel monkeys.
abstract: BACKGROUND
  Benzodiazepines (BZs) are effective anxiolytics and hypnotics, but their use is limited by unwanted side effects, such as motor impairment.
  
  
  OBJECTIVE
  To assess the contribution of alpha1 subunit-containing gamma-aminobutyric acid(A) (GABA(A)) receptor subtypes to the motor-impairing effects of BZs, the present study evaluated two observable measures of motor coordination (balance on a pole, resistance to hind-limb flexion) engendered by nonselective and selective BZ-site agonists in squirrel monkeys.
  
  
  METHODS
  Multiple doses of nonselective BZs (triazolam, alprazolam, diazepam, and chlordiazepoxide) and alpha1 subunit-preferring agonists (zolpidem and zaleplon) were administered to adult male squirrel monkeys (N = 4-6), and experimenters rated the monkey's ability to balance on a horizontal pole ("ataxic-like effects"), as well as the degree of resistance to hind-limb flexion ("myorelaxant-like effects").
  
  
  RESULTS
  Administration of all BZ-type drugs resulted in ataxic-like and myorelaxant-like effects. Pretreatment with the alpha1 subunit-preferring antagonist beta-carboline-3-carboxylate-t-butyl ester (betaCCT) attenuated the ataxic-like effects engendered by both types of drugs. However, betaCCT was largely ineffective at blocking the ability of both BZs and non-BZs to induce myorelaxant-like effects.
  
  
  CONCLUSIONS
  These experiments demonstrate dose-dependent motor impairment in squirrel monkeys using quantitative behavioral observation techniques. Altogether, these findings suggest a lack of a prominent role for alpha1 subunit-containing receptors in the alteration of hind-limb flexion, a putative measure of myorelaxation, induced by BZ-type drugs in monkeys.
authors.affiliation: McLean Hospital/Harvard Medical School, Belmont, MA, USA.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Licata
authors.forename: Donna M
authors.initials: DM
authors.lastname: Platt
authors.forename: James M
authors.initials: JM
authors.lastname: Cook
authors.forename: Michael L
authors.initials: ML
authors.lastname: Van Linn
authors.forename: James K
authors.initials: JK
authors.lastname: Rowlett
mesh_terms: D000818:Animals; D001259:Ataxia / Q000139:chemically induced* / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000378:metabolism*; D012453:Saimiri
chemical_list: D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D001569:Benzodiazepines