SELECTIVE INVOLVEMENT OF CENTRAL 5-HT2 RECEPTORS IN THE MAINTENANCE OF TOLERANCE TO ETHANOL BY ARGININE(8)-VASOPRESSIN

Arginine(8)-vasopressin (AVP) has been shown repeatedly to affect lear ning and memory and to maintain tolerance to ethanol if the brain sero tonin and catecholamine systems are intact. In the present study, 5,7- dihydroxytryptamine (5,7-DHT) was injected intracerebroventricularly t o disrupt serotonergic projections from the raphe to the forebrain. Th is resulted in a marked decrease in 5-hydroxytryptamine (5-HT) immunor eactivity in the terminal areas of the septum and the hippocampus, but not in the serotonin-containing neuronal cell bodies in the raphe nuc lei. In control rats, tolerance to the motor-impairing effects of etha nol lasted for only 5 days after the cessation of ethanol treatment bu t could be maintained indefinitely for as long as AVP was given. In th e 5,7-dihydroxytryptamine-lesioned rats, AVP was unable to maintain th e tolerance. Continuous intracerebroventricular infusion of 5-HT resto red the ability of AVP to maintain ethanol tolerance in the lesioned r ats. A selective 5-HT2 agonist (alpha-methylserotonin) was equally eff ective, and a 5-HT3 receptor agonist (2-methylserotonin) was slightly less effective, but the 5-HT1A agonist dipropylaminotetralin (8-hydrox y-dipropylaminotetralin) was totally ineffective in this respect. The results indicate selective involvement of brain 5-HT2 and possibly 5-H T3 receptors in mediating AVP maintenance of tolerance to ethanol but do not pinpoint their specific loci or roles.