CHRONIC ETHANOL INTOXICATION ENHANCES [H-3] CCPA BINDING AND DOES NOTREDUCE A(1) ADENOSINE RECEPTOR FUNCTION IN RAT CEREBELLUM

The effects of acute and chronic treatment with ethanol on the functio n of A(1) adenosine receptor in the rat cerebellar cortex were investi gated. Acute administration of ethanol (0.5-5 g/kg) had no effect on t he binding of the A(1)-receptor agonist [H-3]2-chloro-N-6-cyclopentyla denosine ([H-3]CCPA) or that of the antagonist [H-3]8-cyclopentyl-1-3- dipropylxanthine ([H-3]DPCPX) in rat cerebellar cortical membranes. Ra ts were rendered ethanol dependent by repeated forced oral administrat ion of ethanol (12-18 g/kg per day) for 6 days. [H-3]CCPA binding was increased by 23% in cerebellar cortical membranes prepared from rats k illed 3 h after ethanol withdrawal compared with saline-treated animal s. The increase in [H-3]CCPA binding was still apparent 12-24 h after the last ethanol administration, but was no longer detectable 3-6 days after ethanol withdrawal. In contrast, the binding of [H-3]DPCPX was not modified in the cerebellar cortex of rats killed at various times after ethanol withdrawal. The acute administration of CCPA [0.25-1 mg/ kg, intraperitoneally (IP)] suppressed the tremors and audiogenic seiz ures apparent 24 h after ethanol withdrawal. Moreover, repeated coadmi nistration of CCPA (0.5 mg/kg, IP, four times daily) and ethanol did n ot prevent the generation of audiogenic seizures during withdrawal but completely prevented mortality. Finally, CCPA antagonized with simila r potencies and efficacies the isoniazid-induced convulsions observed in control and ethanol-withdrawn rats. These results indicate that lon g-term treatment with intoxicating doses of ethanol enhances [H-3]CCPA binding but does not reduce the anticonvulsant efficacy of CCPA or th e function of A(1) adenosine receptors.