Oxytocin Attenuates the Endocrine Disrupting Effects of Cocaine in the Female Rat

Current research indicates that women may exhibit greater susceptibility to cocaine use disorder. Cocaine's endocrine-disrupting effects, including acute impacts on gonadal hormones and chronic disruption of the estrous and menstrual cycles in rodents and humans, may contribute to this susceptibility; however, treatment options for endocrine dysfunction following cocaine exposure remain unexplored. We, and others, have highlighted oxytocin's (OXT) potential to mitigate cocaine use disorder-like behaviors, particularly in females.

We used female, intact and/or ovariectomized (OVX) Sprague-Dawley rats to investigate OXT's potential as a therapeutic agent for cocaine's acute and chronic endocrine disrupting effects. In acute studies, rats received OXT (0.3 mg/kg intraperitoneally, 30 minutes prior) or saline and cocaine (10 mg/kg intraperitoneally, 15 minutes prior) or saline before tail vein blood draw. In chronic studies (6 weeks), rats received cocaine or saline daily, and OXT or saline every 10 days to assess the effects of cocaine and OXT treatment on the estrous cycle. Serum samples were analyzed using enzyme-linked immunosorbent assays for progesterone (P4), estradiol (E2), and OXT levels.

Acute cocaine spiked circulating P4 and E2, an effect that was mitigated by OXT pretreatment. Chronic cocaine administration decreased circulating P4 while increasing circulating E2 and significantly disrupted estrus cycling. Exogenous OXT restored P4 and E2 to precocaine baselines and similarly reversed concurrent effects on estrus cycle dysfunction.

Our results show that OXT may therefore act as a defense against cocaine-induced endocrine disruption, reducing its impact on estrous cycle instability. Thus, OXT is a potential treatment for the endocrine-disrupting effects of cocaine.