P-62DOES SUSCEPTIBILITY TO ALCOHOL BEHAVIORAL SENSITIZATION ALTER OPERANT SELF-ADMINISTRATION AND MOTIVATION FOR ALCOHOL?

Ethanol-induced behavioral sensitization (EIBS) is thought to play a role in drug taking behavior and relapse after abstinence. However, the exact role of sensitization and the vulnerability to its development in addiction phenotypes remains poorly understood. Until recently, some studies have investigated addictive behaviors in mice either prone or resistant to EIBS. Data are now available regarding the correlation between sensitization score and other phenotypes and regarding different addictive phenotypes when comparing sensitized mice and resistant mice. In this context, we have investigated to our knowledge for the first time, the operant ethanol self-administration level and the motivation to self-administer alcohol (breakpoint) depending on the vulnerability to develop sensitization: i.e. in both EIBS resistant and EIBS prone outbred Swiss mice. To induce EIBS, mice were treated once a day with 2.5 g ethanol/kg during 10 days and challenged with the same dose of ethanol 7 days later. EIBS was characterized by a significant increase in locomotion between the challenge day and day 1 and then considered as the ‘EIBS prone’ group. When the difference was not significant mice were considered as the ‘EIBS resistant’ group. Mice were then trained to self-administer 20% ethanol solution in response to one active nose poke (the other one being inactive) on a FR2 schedule. Motivation was assessed with a progressive ratio schedule. Our results show that both operant self-administration level and motivation are dependent upon the sensitization phenotype. These results confirm that EIBS vulnerability is crucial in the development of addictive behaviors.