Cerebellar GABAA receptor binding and function in vitro in two rat lines developed for high and low alcohol sensitivity.

The Bmax of the [3H]muscimol binding in the cerebellum of ethanol-naive alcohol-sensitive ANT (Alcohol Non-Tolerant) rats was only about 70% of that in the alcohol-insensitive AT (Alcohol Tolerant) rats. There were no line differences in the muscimol binding to cerebrocortical and hippocampal membranes. In the alcohol-sensitive rats, the cerebellar [3H]muscimol binding (5 nM) negatively correlated with the ethanol-induced motor-impairment measured in the tilting plane test. Muscimol stimulated the flux of 36Cl- in cerebellar synaptoneurosomes and non-filtered microsacs to the same extent in both rat lines. Ethanol produced only a small, although statistically significant, enhancement of the muscimol-stimulated chloride flux in both rat lines. The present data confirms our earlier finding of a low level of muscimol binding in the cerebellar membranes of alcohol-sensitive rats as compared to alcohol-insensitive rats. Further studies are needed to determine the relationship between the Cl- flux stimulation by muscimol and the differential muscimol binding in the cerebellum of these rat lines, and its importance for alcohol sensitivity.