title: Vasopressin-like peptides retain ethanol tolerance in the absence of changes in serotonin synthesis in limbic structures.
abstract: 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.
mesh_terms: D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism*; D006834:Hydrazines / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012688:Septum Pellucidum / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*
chemical_list: D006834:Hydrazines; D001127:Arginine Vasopressin; D012701:Serotonin; C015119:argipressin, des-GlyNH2(9)-; D000431:Ethanol; D006897:Hydroxyindoleacetic Acid; C004297:3-hydroxybenzylhydrazine; D006916:5-Hydroxytryptophan