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Diazepam sensitizes mice to FG 7142 and reduces muscimol-stimulated36Cl−flux

Authors
Journal
Pharmacology Biochemistry and Behavior
0091-3057
Publisher
Elsevier
Publication Date
Volume
33
Issue
2
Identifiers
DOI: 10.1016/0091-3057(89)90531-5

Abstract

Abstract Chronic treatment with benzodiazepine receptor agonists increases sensitivity to the convulsant action of FG 7142, an inverse agonist. We investigated wheter or not changes in the number and function of GABA-gated chloride channels accompanies this increased sensitivity. Diazepam, 5 mg·kg −1, was thereafter. At 24 hours after the last diazepam dose, 10 of 15 mice had clonic seizures following FG 7142 and four of the remaining five had myoclonic jerks. At 48 hours, only one of six mice developed a clonic seizure, and none were observed in mice tested at 96 or 144 hours. Muscimol-stimulated chloride flux was reduced in cortical synaptosomes from diazepam-treated mice at 24 hours but not at 48 or 96 hours. However, the binding of [ 35S]TBPS, a ligand closely associated with the chloride channel, was unchanged at 24 hours. These results suggest that a transient diminution in GABA-gated chloride channel function, unaccompanied by a reduction in channel number, may underlie the sensitization to the convulsant action of FG 7142 observed after withdrawal from chronic diazepam treatment.

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