Hormonal contraceptives and reward in female rats

Chronic treatment with ethinyl-estradiol (EE) and levonorgestrel (LNG), two of the synthetic steroids in the hormonal contraceptive (HC) pill, decreases brain and plasma levels of progesterone and its neuroactive metabolite allopregnanolone in female rats. Given that allopregnanolone regulates emotional state, cognition and reward, and that cannabis consumption is increasing in young women, we evaluated whether co-exposure to HC and cannabis might affect behavior in female rats. Daily subcutaneous treatment with EE-LNG (0.020-0.060 mg/rat) and a concomitant intravenous infusion of WIN 55,212-2 (12.5 ?g/kg) for 4 weeks did not significantly alter locomotor activity, anxiety-like behavior in the elevated plus maze test, neophobia in the marble burying test, depressive-like behavior in the forced swim test, cognition in the novel object recognition test or sensorimotor gating in the prepulse inhibition test, suggesting that HC do not interact with low, rewarding doses of cannabinoids at behavioral level in young female rats.When assessed on self-administration of palatable food, we found that chronic EE-LNG treatment increased food intake, an effect that was not associated to changes in leptin and ghrelin plasma levels, thus suggesting that the effect of HC might be related to the reward system. In support of this hypothesis, we further observed an increase in dopamine content in ventral hippocampus, nucleus accumbens and prefrontal cortex of EE-LNG-treated rats vs. vehicle-treated rats in the diestrus 1 phase of the estrous cycle, strengthening the hypothesis that HC might target the reward system. Future studies will explore the neurobiological mechanisms involved in HC actions on behavior ad reward.