Vasopressin-like peptides retain ethanol tolerance in the absence of changes in serotonin synthesis in limbic...

Central tolerance to the effects of ethanol in rats can be prolonged beyond its normal time of disappearance by administration of vasopressin (AVP) or desglycinamide-arginine-vasopressin (DGAVP) after ethanol withdrawal. While the mechanism underlying this effect is unknown, we have reported that specific depletion of hippocampal serotonin (5-HT) prevents the prolongation of tolerance by DGAVP. The present study explored possible presynaptic interactions between DGAVP and 5-HT terminals in the hippocampus, in relation to tolerance retention. When administered acutely, DGAVP had no effect on the rates of hippocampal or septal 5-HT synthesis in naive rats, as assessed by the NSD 1015 method. Moreover, chronic DGAVP treatment that maintained tolerance did not change the in vivo rate of 5-HT synthesis in the hippocampus or septum. Similarly, no significant differences were found in the levels of hippocampal 5-HT or 5-HIAA. Septal 5-HIAA levels were slightly but significantly lower in ethanol-DGAVP than in ethanol-saline rats. In vitro studies revealed, on the other hand, that addition of AVP to the incubation medium failed to affect the spontaneous and stimulated release of endogenous 5-HT from hippocampal slices. While the lack of changes in hippocampal 5-HT synthesis argues against a presynaptic DGAVP-5-HT interaction, the possibility remains of a peptide modulation of 5-HT postsynaptic actions.