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Flumazenil but not FG7142 reverses the decrease in pentobarbital sleep caused by activation of central noradrenergic
K Matsumoto1, S I Kohno, K Ojima
1Department of Pharmacology, Research Institute for Wakan-Yaku, Toyama Medical and Pharmaceutical University, Japan. mkinzo@ms.toyama-mpu.ac.jp
Brain Research
|April 18, 1997
Summary
Central noradrenergic systems modulate pentobarbital sleep. This study investigated the role of GABA(A)/benzodiazepine receptors, finding that endogenous ligands with inverse agonist properties influence this interaction in mice.
Area of Science:
- Neuropharmacology
- Sleep Research
Background:
- Central noradrenergic systems modulate pentobarbital-induced hypnosis.
- The GABA(A)/benzodiazepine receptor system is a key target for hypnotic drugs.
Purpose of the Study:
- To investigate the involvement of the GABA(A)/benzodiazepine receptor system in the reduction of pentobarbital sleep by central noradrenergic activation.
- To examine the effects of benzodiazepine receptor ligands on pentobarbital sleep and adrenoceptor modulation.
Main Methods:
- Administered alpha1-adrenoceptor agonist (methoxamine) and alpha2-adrenoceptor antagonist (yohimbine) intracerebroventricularly (i.c.v.) in mice.
- Assessed effects of benzodiazepine receptor ligands (flumazenil, FG7142) on pentobarbital-induced sleep.
- Evaluated interactions between adrenoceptor ligands and benzodiazepine receptor ligands on sleep duration.
Main Results:
- Methoxamine and yohimbine dose-dependently decreased pentobarbital sleeping time.
- Flumazenil (benzodiazepine receptor antagonist) had no effect on pentobarbital sleep.
- FG7142 (benzodiazepine receptor inverse agonist) shortened pentobarbital sleep.
- Flumazenil reversed the sleep-shortening effects of methoxamine and yohimbine.
- FG7142 did not affect methoxamine- or yohimbine-induced sleep reduction.
Conclusions:
- The GABA(A)/benzodiazepine receptor system is implicated in the noradrenergic modulation of pentobarbital sleep.
- Endogenous benzodiazepine receptor ligands with inverse agonist properties likely mediate the effects of methoxamine and yohimbine on pentobarbital sleep duration.