Interaction between des-glycinamide9-[Arg8]vasopressin and serotonin on ethanol tolerance

Sham and electrolytic lesions of the dorsal, median, and dorsal + median raphe nuclei were made in different groups of rats. One week later, daily oral treatment with ethanol (5 g/kg p.o. for 25 days) was started. This treatment produced tolerance to the hypothermic and motor impairing (moving belt test) effects of ethanol. On day 26, ethanol was stopped and subcutaneous injection of either 10 micrograms of des-Gly9-[Arg8]vasopressin (DGAVP) in saline or saline alone was started. The retention of tolerance to ethanol was measured at 3-day intervals for both hypothermia and motor-impairment. In sham-saline groups, disappearance of tolerance took 3 days for the hypothermic effect, and 9 days for the motor-impairment effect. Tolerance to both effects, however, was still observed after 9 days in DGAVP-treated rats with either sham or dorsal raphe lesions. Peptide treatment, on the other hand, failed to maintain tolerance in rats with median or median + dorsal raphe lesions. These results suggest that an intact mesolimbic serotonin pathway is necessary for the action of DGAVP on the retention of ethanol tolerance.