1329785

Functional alterations in cerebral GABAA receptor complex associated with formation of alcohol dependence: analysis using GABA-dependent 36Cl- influx into neuronal membrane vesicles.

Article date: 1992/7/1

PubMed ID: 1329785

Journal name: Alcohol and alcoholism (Oxford, Oxfordshire) (ISSN: 0735-0414)

ABSTRACT

The effect of alcohol dependence induced by ethanol inhalation on GABA-dependent 36Cl- influx into membrane vesicles prepared from the mouse brain has been examined. Ethanol, flunitrazepam and salsolinol induced a significant facilitation of the GABA-dependent 36Cl- influx into membrane vesicles obtained from the normal mouse brain. Ethanol inhalation induced the facilitation of GABA-dependent 36Cl- influx at 3-12 hr after the initiation of inhalation, but this facilitation returned to a normal level within 12 hr. In membrane vesicles obtained from the brain of an alcohol-dependent mouse at 7 days after the initiation of ethanol inhalation, not only was there a significant decrease of the GABA-dependent 36Cl- influx but there occurred also the disappearance of the activating effects of ethanol, flunitrazepam and salsolinol on the influx. This decrease in GABA-dependent 36Cl- influx was found to be recovered within 8 hr after the withdrawal of ethanol inhalation. On the other hand, behavioural withdrawal signs such as tonic-clonic convulsions with grimaces and heads thrown back appeared at 8 hr after the withdrawal of ethanol inhalation and continued for 8-16 hr. These results suggest that the observed functional deteriorations at cerebral GABAA receptors such as the decrease of GABA-dependent 36Cl- influx and the disappearance of the activating effects of ethanol, flunitrazepam and salsolinol on the influx may contribute to the preparation of the exhibition of ethanol withdrawal signs and/or the establishment of functional tolerance to alcohol, but are not directly related to the exhibition of alcohol withdrawal signs.

This document is available from: http://directlinks.cc/files/muscimol/1329785.pdf

Author List: Kuriyama K, Ueha T

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

Substances mentioned in the article: Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Chlorides; Receptors, GABA-A; Muscimol; gamma-Aminobutyric Acid; Flunitrazepam; tert-butylbicyclo-2-benzoate;

Mesh terms: Administration, Inhalation; Alcohol Withdrawal Delirium/physiopathology; Alcoholism/physiopathology; Animals; Brain/physiopathology; Bridged Bicyclo Compounds/pharmacokinetics; Bridged Bicyclo Compounds, Heterocyclic; Chlorides/metabolism; Flunitrazepam/pharmacokinetics; Male; Mice; Mice, Inbred Strains; Muscimol/pharmacokinetics; Neurons/drug effects; Radioligand Assay; Receptors, GABA-A/drug effects; Synaptic Membranes/drug effects; Synaptic Vesicles/drug effects; gamma-Aminobutyric Acid/physiology;

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