Characterization of the behavioral sensitization and the conditioned response induced by long-term exposure to alcohol in DBA/2J and Swiss mice.

Repeated administrations of addictive drugs induce gradual changes in some of their behavioral effects. This phenomenon is called “behavioral sensitization”. In laboratory rodents, drug-induced behavioral sensitization is generally modeled as a progressive increase in the locomotor stimulant effects over repeated administrations of the same drug dose. Chronic exposure to ethanol has been shown to induce a strong and robust sensitization in mice. Very few studies were published on the behavioral aspects of ethanol-induced sensitization, especially regarding the procedural and environmental parameters influencing its development and expression (duration of the process). Therefore, little is known about the time course of ethanol sensitization after an extensive exposure exceeding a few days. The first aim of the present study was to better characterize the development and expression of ethanol sensitization after an extended exposure to 45 daily injections. Does ethanol sensitization continue to develop at the same rate after the first few days of ethanol administrations ? Does it reach a ceiling effect? Does it even start to decline after reaching a peak level? The second aim was to test whether ethanol sensitization results in a conditioned increase in locomotor activity when sensitized mice are tested after a saline injection in the testing environment. The results of the present study show that ethanol sensitization continues to develop beyond 20 days to reach maximal levels after about 25 injections in DBA2/j mice and 40 injections in Swiss mice, although the core phase of the development of ethanol sensitization occurred in both strains during the first 20 days. The present results extend previous reports indicating that sensitization to the stimulant effects of ethanol does not induce an excitatory conditioned response, even after 46 associations of a specific context with ethanol injections. The extensive exposition to ethanol in the present study makes it very unlikely that the lack of conditioned response was due to an insufficient pairing of the test context with ethanol injections.