Oxytocin blocks the environmentally conditioned compensatory response present after tolerance to ethanol-induced hypothermia in mice.

The present study tested the hypothesis that the attenuation by oxytocin of tolerance to ethanol-induced hypothermia relies upon an impairment of the putative conditioning processes underlying environment-specific tolerance. According to the conditioning model of tolerance, such tolerance occurs because an opposite compensatory response conditioned to ethanol-paired cues attenuates ethanol's effects. Tolerance to ethanol-induced hypothermia was established to a particular environment over 4 days by injecting mice (daily) with oxytocin 2 h before ethanol, outside the colony room. As controls, other mice were injected similarly but following testing in the animal room. We found that oxytocin suppressed the conditioned compensatory response, revealed by injecting saline to every group in the tolerance-associated environment. These results suggest that oxytocin acted, at least partly, via an inhibition of the associative learning processes that facilitate tolerance development.