Abstract | RATIONALE: Delineation of the receptor mechanisms underlying the behavioral effects of benzodiazepines should allow for the development of drugs with improved clinical utility and reduced side effects. OBJECTIVES. The purpose of the present study was to investigate the role of GABAA/alpha1 receptors in the sedative and motor-impairing effects of benzodiazepines. METHODS: Squirrel monkeys were tested with the GABAA/alpha1-preferring agonist zolpidem and the nonselective benzodiazepine agonist triazolam alone and in combination with the GABAA/alpha1-preferring antagonist beta-CCt and the nonselective benzodiazepine antagonist flumazenil. During 30-min experimental sessions, all occurrences of normal behaviors like locomotion, environment- and self-directed behaviors, as well as side effects such as ataxia, rest and procumbent postures were scored. RESULTS: CONCLUSIONS: GABAA/alpha1 receptor mechanisms appear to play a key role in the ataxic effects of benzodiazepine agonists in squirrel monkeys, similar to recent results with transgenic mice. In contrast to the findings of these recent studies, GABAA mechanisms other than or in addition to those mediated at the alpha1 subunit may play a more important role in the sedative/ hypnotic effects of benzodiazepines in squirrel monkeys.
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Authors | Donna M Platt, James K Rowlett, Roger D Spealman, James Cook, Chunrong Ma |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 164
Issue 2
Pg. 151-9
(Nov 2002)
ISSN: 0033-3158 [Print] Germany |
PMID | 12404077
(Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Carbolines
- GABA Agonists
- GABA Modulators
- GABA-A Receptor Antagonists
- Pyridines
- Receptors, GABA-A
- Benzodiazepines
- Triazolam
- Flumazenil
- Zolpidem
- tert-butyl beta-carboline-3-carboxylate
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Topics |
- Animals
- Ataxia
(chemically induced, drug therapy)
- Benzodiazepines
(antagonists & inhibitors, pharmacology)
- Carbolines
(pharmacology)
- Dose-Response Relationship, Drug
- Drug Interactions
- Flumazenil
(pharmacology)
- GABA Agonists
(adverse effects, pharmacology)
- GABA Modulators
(adverse effects, pharmacology)
- GABA-A Receptor Antagonists
- Male
- Motor Activity
(drug effects, physiology)
- Pyridines
(adverse effects, pharmacology)
- Receptors, GABA-A
(classification, drug effects, physiology)
- Saimiri
- Social Behavior
- Triazolam
(adverse effects, pharmacology)
- Zolpidem
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