Sex Comparison of Drug‐seeking Behavior after Limited‐Access Methamphetamine‐taking in a Socio‐sexual Context in Rats

Abstract

Vulnerability to develop a substance use disorder is influenced by social context, including sexual experience, in both male and female drug users. Methamphetamine (Meth) is associated with increased sexual pleasure, driving further drug use. Our laboratory has demonstrated in male rats that limited access to Meth in a socio‐sexual context during consecutive daily sessions enhances drug‐seeking behavior during extinction and reinstatement tests. The goal of this study was to investigate the effects of Meth‐taking in a socio‐sexual context in female rats, which differ from males in behavioral and pharmacological responses to Meth in an estrus‐cycle dependent manner. Female Sprague Dawley rats were ovariectomized and implanted with IV catheters. They underwent 5 sessions of limited‐access Meth self‐administration (maximum drug intake 1 mg/kg/session) each separated by three days. Two days and 4 hours prior to each session, females received estradiol benzoate (10μg) and progesterone (500μg) respectively. Females either mated immediately after each session (concurrent females, n=7) or were returned to home cage (Meth only females, n=7). The male mating partners of the concurrent females were also tested for operant behavior (concurrent males, n=8) to determine whether concurrent Meth self‐administration and mating only once every four days is sufficient to enhance drug‐seeking behavior. After Meth self‐administration, all groups underwent 8 operant extinction sessions followed by cue reinstatement. Both concurrent groups (female and male) readily acquired Meth self‐administration, while Meth only females were delayed in acquiring Meth self‐administration compared to concurrent females. No differences in operant behavior were detected between groups during extinction. Next, it was determined that both female groups exhibited significant cue‐induced reinstatement of drug‐seeking behavior with no effects of prior concurrent sex behavior. In contrast, concurrent males did not significantly reinstate drug‐seeking. Together these results suggest that Meth‐taking in a socio‐sexual context may facilitate initial drug‐taking behavior in female rats, and that females have a higher vulnerability to relapse than males. However, the lack of enhanced vulnerability to relapse due to concurrent sexual behavior in concurrent males suggests that imposing a 3‐day interval between sessions mitigated the development of addiction‐like behavior in this model compared to our previous findings using daily sessions. Therefore, potential effects of concurrent socio‐sexual behavior may have also gone undetected in females using the current experimental design. Findings here provide useful insight into behavioral responses to limited‐access Meth self‐administration in female rats, however further development of experimental procedures is necessary to investigate the effect of Meth‐taking in a socio‐sexual context on extinction and relapse behavior in females.Support or Funding InformationSupported by Institutional Research Support Program at University of Mississippi Medical Center.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.