CHRONIC ETHANOL AND PENTOBARBITAL ADMINISTRATION IN THE RAT - EFFECTS ON GABA-A RECEPTOR FUNCTION AND EXPRESSION IN BRAIN

Chronic exposure of rats to ethanol significantly decreases GABAA receptor-mediated 36Cl- uptake in cerebral cortical synaptoneurosomes. Muscimol and pentobarbital stimulation as well as ethanol enhancement of muscimol-stimulated 36Cl- flux are significantly decreased following chronic ethanol inhalation. Repeated pentobarbital administration has a similar effect on muscimol and pentobarbital-stimulated 36Cl- uptake in cerebral cortical synaptoneurosomes. We have postulated that these adaptive responses may be associated with an alteration of GABAA receptor gene expression. Chronic ethanol exposure resulted in a significant reduction in the levels of GABAA receptor α-subunit mRNA's. The most abundant mRNA species in the rat cerebral cortex were reduced 40-50% (4.4 Kb mRNA, 43%, 4.8 Kb mRNA, 47%) β-Actin mRNA and poly(A)+ RNA levels were not significantly reduced following chronic ethanol exposure. Repeated pentobarbital administration had no effect on the level of the 4.4 and 4.8 Kb transcripts of α-subunit mRNAs in rat cerebral cortex. These data suggest that chronic ethanol exposure alters the level of mRNA's coding for the α-subunit of the GABAA receptor. This decrease may reflect an alteration of mRNA processing in the cell or an alteration in GABAA receptor gene expression. © 1990.