The effects of neurohypophyseal hormones on tolerance to the hypothermic effect of ethanol.

Mice were made tolerant to the hypothermic effect of ethanol by repeated administration of ethanol (4 g/kg, 25% v/v, IP) on three consecutive days. The colonic temperature was measured in individually-housed animals immediately before and 45 min after ethanol treatment. Peptide treatments with various schedules were made SC 2 hr before the first ethanol challenge. The decrease in hypothermic response was accepted as a tolerance phenomenon, which developed in control animals by day 2. A single injection of oxytocin (OXT) or lysine vasopressin (LVP [0.1 or 1 IU peptide] animal) before the first ethanol injection did not change the initial sensitivity to ethanol. This absence of acute interactions is also reflected in the sleep onset and sleep duration after 5 g/kg ethanol (IP). In contrast, both OXT and LVP affected the development of tolerance. Repeated treatments with graded doses of OXT (0.5-2 IU) or LVP (0.25-1 IU) every day for 3 days blocked the development of tolerance. 0.002 IU LVP facilitated the development of hypothermic tolerance. The remaining doses of the peptides were ineffective. A high dose of LVP (1 IU) facilitated hypothermic tolerance if the peptide was injected when tolerance to ethanol had developed fully without previous peptide treatment. OXT, on the other hand, was ineffective in this particular experimental model. The data suggest that both neurohypophyseal hormones (LVP and OXT) block the early developmental phase of tolerance to ethanol. On the other hand, LVP facilitated the expression of tolerance if the peptide was given to mice with fully developed tolerance.