| Title | Contribution of alpha1 subunit-containing gamma-aminobutyric acid(A) (GABA (A)) receptors to motor-impairing effects of benzodiazepines in squirrel monkeys. | | Author(s) | Licata SC, Platt DM, Cook JM, Van Linn ML, Rowlett JK | | Institution | McLean Hospital/Harvard Medical School, Belmont, MA, USA. | | Source | Psychopharmacology (Berl) 2008 Nov 25. | | Abstract | RATIONALE: Benzodiazepines (BZs) are effective anxiolytics and hypnotics, but their use is limited by unwanted side effects, such as motor impairment.
OBJECTIVES: 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.
MATERIALS AND 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19031072 |
|
