Cockrell Carlee M, Cox Ariel L, Berry Melanie, Kohtz Amy S
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Department of Biological Sciences, William Carey University, Hattiesburg, MS 39401, USA.
Endocrinology. 2025 May 19;166(7). doi: 10.1210/endocr/bqaf096.
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.
当前研究表明，女性可能对可卡因使用障碍表现出更高的易感性。可卡因的内分泌干扰作用，包括对性腺激素的急性影响以及对啮齿动物和人类发情周期和月经周期的慢性干扰，可能是导致这种易感性的原因；然而，可卡因暴露后内分泌功能障碍的治疗选择仍未得到探索。我们以及其他人都强调了催产素（OXT）减轻可卡因使用障碍样行为的潜力，尤其是在女性中。
我们使用完整和/或卵巢切除（OVX）的雌性Sprague-Dawley大鼠来研究OXT作为治疗可卡因急性和慢性内分泌干扰作用的药物的潜力。在急性研究中，大鼠在尾静脉采血前接受OXT（腹腔注射0.3mg/kg，提前30分钟）或生理盐水，以及可卡因（腹腔注射10mg/kg，提前15分钟）或生理盐水。在慢性研究（6周）中，大鼠每天接受可卡因或生理盐水，每10天接受OXT或生理盐水，以评估可卡因和OXT治疗对发情周期的影响。使用酶联免疫吸附测定法分析血清样本中的孕酮（P4）、雌二醇（E2）和OXT水平。
急性给予可卡因使循环中的P4和E2升高，而OXT预处理减轻了这种作用。长期给予可卡因会降低循环中的P4，同时增加循环中的E2，并显著扰乱发情周期。外源性OXT将P4和E2恢复到可卡因给药前的基线水平，并同样逆转了对发情周期功能障碍的并发影响。
我们的结果表明，OXT可能因此起到抵御可卡因诱导的内分泌干扰的作用，减少其对发情周期不稳定的影响。因此，OXT是治疗可卡因内分泌干扰作用的一种潜在药物。
