Parametric analysis of the development and expression of ethanol-induced behavioral sensitization in female Swiss mice: effects of dose, injection schedule, and test context

Repeated administrations of ethanol induce a progressive and enduring increase in its locomotor stimulant effects, a phenomenon termed behavioral sensitization that has not been systematically characterized. The aim of the present studies was to characterize the development and expression of ethanol sensitization in female Swiss mice by examining (1) the doses of ethanol that induce behavioral sensitization, (2) the doses of acute ethanol challenges that are necessary to express behavioral sensitization, (3) the effects of the intervals between administrations, and (4) the context dependency of ethanol sensitization. Mice were i.p. injected for 8 days with various ethanol doses, and locomotion was recorded for 5 min. Two days after the last sensitization session, ethanol sensitization was tested in 30-min test sessions. Mice repeatedly injected with 2.5 g/kg ethanol showed a progressive (200-300%) increase in locomotor activity. In response to a 2.5 g/kg ethanol challenge, the mice repeatedly treated with doses above 1.5 g/kg showed a significant sensitization. Following the induction of sensitization with the maximally effective sensitizing dose (2.5 g/kg), mice showed greater activation after challenges with 1.5, 2.0, 2.5, and 3.0 g/kg ethanol. The intervals (24, 48, or 96 h) between ethanol injections did not affect the induction or expression of sensitization. Finally, sensitization to 2.5 g/kg ethanol was expressed regardless of the context in which it was induced. Female Swiss mice develop a robust context-independent sensitization after repeated ethanol injections at all doses above 1.5 g/kg, including highly sedative doses such as 4 g/kg.