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.
Bibliographical noteFunding Information:
Acknowledgements The authors are grateful to Erin Larson, Annemarie Loth, Brooks Simning and Will Oudavanh for their technical assistance, and to Andrew D. Morgan for critically evaluating initial drafts of this manuscript. This study was supported by NIDA grants R01 DA03240 and K05 DA15267 (M.E.C.) and grant F31 DA14161 (M.E.R.).
- Sex differences