Functional alterations in GABAA receptor complex induced by ethanol.

Possible direct actions of ethanol on cerebral GABAA receptor complex have been analyzed using purified GABAA receptor complex from the bovine cerebral cortex and its reconstituted vesicles. Addition of ethanol to the reconstituted vesicles with purified GABAA receptor complex induced a significant increase of GABA-dependent 36Cl- influx. Furthermore, the reconstituted GABAA receptor pretreated with 20 mM ethanol, which had no effect on GABAA receptor binding, also showed an increase of the GABA-dependent 36Cl- influx. On the other hand, the GABA-dependent 36Cl- influx into membrane vesicles prepared from alcohol dependent mouse brain showed a significant decrease, although this decrease was found to be recovered at 8 hours after the withdrawal of ethanol inhalation. Moreover, the expression of mRNA for GABAA receptor alpha 1-subunit in the brain showed an elevation in alcohol dependent condition, although this elevation was recovered to the control level after the withdrawal of alcohol inhalation. The present results suggest that continuous inhalation of ethanol in vivo may induce not only the alterations in the function of GABAA receptor complex but also that in the expression of mRNA for the receptor in the brain.