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.