Site of interaction of serotonin and desglycinamide-arginine-vasopressin in maintenance of ethanol tolerance.

Rats trained to walk in a moving belt apparatus were subjected to a partial (fornix-fimbria (FF] or total (fornix-fimbria + cingulum bundles (FF + CB] chemical denervation of the dorsal serotonergic afferent pathways to the hippocampus. After chronic alcohol treatment that resulted in tolerance development to the motor-impairing effects of ethanol, desglycinamide-arginine8-vasopressin (DGAVP) or saline treatment was started and the residual tolerance measured at several intervals after ethanol withdrawal. DGAVP administration resulted in a virtually complete retention of ethanol tolerance when given to sham-operated controls or FF-lesioned rats. The peptide treatment failed, however, to prolong tolerance in rats bearing a complete FF + CB lesion, that reduced serotonin (5-HT) levels in the hippocampus and overlying parietal cortex to 10 and 45% of controls respectively. These results suggest that the serotonergic innervation of these areas is necessary for the action of DGAVP in the maintenance of ethanol tolerance.