Sex differences in incentive-sensitization produced by intermittent access cocaine self-administration

Rationale Intermittent Access (IntA) cocaine self-administration, which models intermittent patterns of cocaine use in humans during the transition to addiction, is especially effective in producing incentive-sensitization and other addiction-like behavior in male rats. However, female rats show more robust psychomotor sensitization than males, and following initial use, women develop problematic patterns of drug use more readily than men. We hypothesized, therefore, that female rats might be more susceptible to the incentive-sensitization produced by IntA experience. Objective To assess changes in motivation for cocaine, using a behavioral economic indicator of cocaine demand (“elasticity” of demand curves), and other addiction-like behavior, as a function of IntA cocaine self-administration experience in male and female rats. Results IntA experience produced a progressive increase in motivation for cocaine in both males and females, as indicated by a decrease in the elasticity of cocaine demand curves, and this persisted undiminished following 14 days of abstinence. However, IntA produced a more rapid and greater increase in motivation for cocaine (incentive-sensitization) in females than males. Females also consumed more cocaine than males, although this did not predict changes in motivation. On the other hand, there were no sex differences in the preferred level of cocaine consumption when cost was low ( Q 0 ), nor in cocaine- or cue-induced reinstatement of drug-seeking behavior. Conclusions The observation that females are more susceptible to incentive-sensitization when intermittently exposed to cocaine may provide a mechanism for the more rapid development of problematic drug use in females (“telescoping effect”) reported in clinical studies.