Adolescent cannabinoid treatment negatively affects reproductive behavior in female rats

Sex differences in the neurobehavioral effects of chronic cannabinoid exposure suggest that gonadal hormones may modify cannabinoid activity. The current experiment assessed the impact of combined cannabinoid and estradiol treatment in ovariectomized, adolescent female rats on subsequent adult sexual behavior. Female Long-Evans rats were administered daily injections of either the cannabinoid agonist, CP 55,940 (0.4 mg/kg), or vehicle from post-natal day (PND) 40-49. Half of each treatment group also received daily injections of estradiol (50 μg/kg) or sesame oil vehicle from PND 39-49. Beginning on PND 74, subjects' reproductive behavior, including receptivity, proceptivity, and pacing, was assessed via a fifteen-minute paced mating test. There were significant main effects of estradiol treatment on rate of hop-darts emitted, number of arena crossings, and ejaculations received during the paced mating test. Overall, estradiol-treated females produced higher and more typical levels of sexual behavior. There were significant interactions between hormone and cannabinoid treatment on lordosis quotient, percentage of exits following male sexual stimulation, and contact-return latency for intromissions. Adolescent cannabinoid treatment detrimentally impacted the display of female receptivity and pacing, but only within estradiol-treated subjects. We discuss possible interpretations of these results, including potential mechanisms by which adolescent cannabinoid exposure might disrupt the normal development of female reproductive behavior.