Retention of ethanol tolerance by desglycinamide-arginine-vasopressin occurs in the absence of changes in hippocampal serotonin synthesis.
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. 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.
Department of Pharmacology, University of Toronto, Ontario, Canada.
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Speisky
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Kalant
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000032:analysis*; D006900:Hydroxylation; D008297:Male; D009068:Movement / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000032:analysis*; D014364:Tryptophan / Q000378:metabolism
D001127:Arginine Vasopressin; D012701:Serotonin; C015119:argipressin, des-GlyNH2(9)-; D000431:Ethanol; D014364:Tryptophan