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.
Uusi-Oukari
M
M
Research Laboratories, Alko Ltd., Helsinki, Finland.
Korpi
E R
ER
D000428:Alcohol Drinking / Q000502:physiology*; D000818:Animals; D002531:Cerebellum / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000378:metabolism / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects; D009118:Muscimol / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism* / Q000502:physiology
D002712:Chlorides; D011963:Receptors, GABA-A; D009118:Muscimol; D000431:Ethanol