Functional properties of GABAA receptors in two rat lines selected for high and low alcohol sensitivity.

Article date: 1992/5/1

PubMed ID: 1318725

Journal name: Alcohol (Fayetteville, N.Y.) (ISSN: 0741-8329)


The effects of lorazepam and sodium barbital on GABAA receptor function were evaluated in rat lines selected for differential sensitivity to the motor-impairing effects of ethanol [alcohol-insensitive (AT) and alcohol-sensitive (ANT) lines]. The effect of GABA on [3H]flunitrazepam and [3H]Ro 15-4513 binding and the effects of lorazepam and sodium barbital on [3H]muscimol binding were measured in cerebellar, cerebrocortical, and hippocampal membrane preparations. The effects of lorazepam and sodium barbital on muscimol-stimulated 36Cl- influx were measured using membrane vesicle suspensions from the same brain areas. No differences were found between the rat lines in the GABA-induced stimulation of [3H]flunitrazepam binding or in the lorazepam and sodium barbital-induced enhancement of either [3]muscimol binding or muscimol-stimulated 36Cl- flux. Neither was desensitization of the 36Cl- flux affected differently by ethanol, lorazepam, and barbital in vitro between the lines. The affinity of cerebellar diazepam-insensitive (DZ-IS) [3H]Ro 15-4513-binding sites for benzodiazepine agonists has been shown to be much greater in the ANT than the AT rats. In the present study, at 0 degrees C, GABA decreased [3H]Ro 15-4513 binding in the presence of diazepam only in ANT rats. Similarly, GABA decreased this binding at 37 degrees C in ANT rats having a high affinity for diazepam, whereas it enhanced the binding in all AT samples in those ANT samples where diazepam had a poor AT-like affinity. The decrease in binding in ANT samples is apparently caused by the enhancing effect of GABA on diazepam binding to DZ-IS [3H]Ro 15-4513-binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

This document is available from: http://directlinks.cc/files/muscimol/1318725.pdf

Author List: Uusi-Oukari M, Korpi E R

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Azides; Chlorides; Receptors, GABA-A; Benzodiazepines; Muscimol; Ethanol; gamma-Aminobutyric Acid; Barbital; Flunitrazepam; Ro 15-4513; Lorazepam;

Mesh terms: Animals; Azides/metabolism; Barbital/pharmacology; Benzodiazepines/metabolism; Brain/metabolism; Cerebellum/metabolism; Chlorides/metabolism; Drug Resistance; Ethanol/pharmacology; Flunitrazepam/metabolism; Lorazepam/pharmacology; Muscimol/metabolism; Rats; Receptors, GABA-A/physiology; Temperature; gamma-Aminobutyric Acid/pharmacology;

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