Tolerance to ethanol and severity of withdrawal in mice are enhanced by a vasopressin fragment

Mice were rendered physically dependent on ethanol by inhalation of ethanol vapour and treatment with pyrazole for 3 days. On Day 4, withdrawal convulsions were measured and on Day 5 or later, residual tolerance to the hypothermic effect of an i.p. challenge dose of 3 g/kg ethanol was assessed. Mice continuously infused with the vasopressin fragment des-Gly⁹-[Arg⁸]-vasopressin dicitrate (DGAVP) throughout the periods of dependence induction and withdrawal testing exhibited exacerbated withdrawal convulsions. DGAVP also tended to exacerbate withdrawal when injected s.c. repeatedly (10 μg/injection/mouse) during testing for withdrawal. The data indicate that these effects were not likely to have been due to subconvulsive activity of DGAVP by itself or to changes in blood levels of ethanol. Continuous infusion of DGAVP enhanced residual tolerance on Day 5 but did not maintain tolerance when the time interval between withdrawal and testing for tolerance was increased. Restricting treatment with DGAVP to the period of induction of dependence (Days 1-3) also enhanced tolerance on Day 5. The data indicate that the vasopressin fragment modulates the development and/or the decay of tolerance to ethanol. In addition it exacerbates withdrawal convulsions, an effect that may be due to modulation of physical dependence.