Cyclic adenosine 3',5'-monophosphate, adenylate cyclase and physical dependence on ethanol: studies with tranylcypromine.

Tranylcypromine, a monoamine oxidase inhititor, was administered to rats during chronic ethanol treatment. The severity of the hyperactive withdrawal behavior observed upon removal of ethanol was, during the first 60 hours of treatment, similar in both ethanol and ethanol + tranylcypromine treated animals. However, after 84 hours of ethanol treatment, tranylcypromine slightly depressed the withdrawal severity. Rises in cerebral cortical cyclic adenosine 3',5'-monophosphate (cAMP) levels and adenylate cyclase activity associated with withdrawal behavior in ethanol-treated rats, though, were not observed. (Adenylate cyclase activity used throughout this paper refers to % conversion of 3H-adenine into 3H-cAMP). Based on this and previous data, a model invoking two neurochemical adaptations--one in adenylate cyclase and one, as yet, unknown-is proposed for the mechanism of physical dependence.