Sex differences in the acquisition of IV methamphetamine self-administration and subsequent maintenance under a progressive ratio schedule in rats

Rationale: Previous work indicates that female rats initiate cocaine use sooner than male rats and reach significantly higher break points (BPs) for a single injection of cocaine under a progressive ratio (PR) schedule compared to male rats. Objectives: The present study extends previous work examining sex differences to the acquisition of methamphetamine (METH) (0.02 mg/ kg) and maintenance of METH-maintained responding under a PR schedule. Methods: An automated priming procedure that has previously been shown to be sensitive to sex differences was used for the acquisition of drug self-administration. A PR schedule that has been shown to be sensitive in detecting sex differences in maintenance levels of cocaine-reinforced responding was used for the maintenance phase of the experiment. Results: A greater percentage of female rats met the acquisition criterion for METH (0.02 mg/kg) self-administration compared to male rats (55.6% versus 11.1%, respectively), and they did so at a significantly faster rate. Under stable fixed-ratio 1 (FR1) conditions (after acquisition and 5 days before the PR schedule) female rats responded for significantly more METH (0.02 mg/kg) infusions compared to males. Dose-response curves obtained under the PR schedule during maintenance indicated that female rats self-administered significantly more METH infusions compared to male rats. Conclusions: These data suggest that female rats are more vulnerable to the acquisition of METH self-administration, and they are more motivated to self-administer METH compared to male rats under a PR schedule during the maintenance phase.