1647704

gamma-Aminobutyric acid-activated chloride channels in rats selectively bred for differential acute sensitivity to alcohol.

Article date: 1991/3/1

PubMed ID: 1647704

Journal name: Alcoholism, clinical and experimental research (ISSN: 0145-6008)

ABSTRACT

Effects of various sedative hypnotic agents on GABA-mediated chloride flux were evaluated in whole brain membrane vesicles (microsacs) prepared from rats selectively bred for high (HAS) and low sensitivity (LAS) to an acute hypnotic dose of alcohol. The HAS rats were more sensitive to the effects of pentobarbital, phenobarbital, flunitrazepam, and ethanol on GABA-mediated chloride flux compared with the LAS rats. No differences between the lines in GABA-stimulated chloride flux were observed. Modulation of 1-[3H]-phenyl-4-butyl-2,6,7-trioxabicyclo(2.2.2)octane ([3H]-TBOB) and [3H]-diazepam binding also was measured. The lines did not differ in inhibition of [3H]-TBOB binding by pentobarbital, phenobarbital, muscimol or picrotoxin. Although the lines displayed almost identical KD and Bmax for [3H]-diazepam binding, the GABA agonist, muscimol, was a more potent stimulator of [3H]-diazepam binding in membranes prepared from HAS rats than from LAS rats. These findings are discussed in light of previous work using other selected lines.

This document is available from: http://directlinks.cc/files/muscimol/1647704.pdf

Author List: Allan A M, Mayes G G, Draski L J

Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.

Substances mentioned in the article: Chloride Channels; Membrane Proteins; Receptors, GABA-A; Picrotoxin; Muscimol; gamma-Aminobutyric Acid; Flunitrazepam; Pentobarbital; Diazepam; Phenobarbital;

Mesh terms: Alcohol Drinking/genetics; Animals; Chloride Channels; Diazepam/pharmacokinetics; Female; Flunitrazepam/pharmacology; Membrane Proteins/drug effects; Muscimol/pharmacology; Pentobarbital/pharmacology; Phenobarbital/pharmacology; Phenotype; Picrotoxin/pharmacology; Rats; Rats, Inbred Strains; Receptors, GABA-A/genetics; Selection, Genetic; gamma-Aminobutyric Acid/physiology;

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