This study was limited to assaying adenosine receptor binding in mice that were chronically treated with ethanol or an adenosine agonist, in collaboration with Dr. M. Saeed Dar of the Department of Pharmacology at East Carolina University School of Medicine. Rats that were tolerant to ethanol were also tolerant to adenosine's accentuation of ethanol-induced motor incoordination. Similarly, mice that were chronically treated with an adenosine receptor agonist showed cross-tolerance to the motor disturbing effects of ethanol. These findings further supported the hypothesis of brain adenosine modulation of ethanol-induced motor impairment. However, no changes were observed in adenosine receptor binding in the cerebellum of mice chronically treated with either an adenosine agonist or ethanol. It is well documented that the A-1 subtype of adenosine receptors is involved in acute ethanol-induced motor dysfunction. Future studies, in collaboration with Dr. Dar, are planned to selectively inhibit translation of the cerebellar A-1 receptor by in vivo administration of antisense DNA to the A-1 receptor mRNA. It is anticipated that depletion of A-1 receptors will result in alleviation of ethanol-induced motor incoordination. The use of antisense DNA could lead to other studies as well. Studies related to the peripheral-type benzodiazepine receptor (PBR) were documented in previous annual reports. These studies are intricately related to the study of contingent tolerance to the anticonvulsant activity of carbamazepine in the amygdala kindling paradigm, as outlined in Research Project # Z01 MH 02459-05 BP. Therefore, studies on the PBR will be reported in that project report.
