Davidson College, Davidson, NC, USA.
Davidson College, Davidson, NC, USA.
Pharmacol Biochem Behav. 2022 Jul;218:173431. doi: 10.1016/j.pbb.2022.173431. Epub 2022 Jul 16.
Ovarian hormones influence the activity of endogenous opioids, and exogenous administration of estradiol reduces opioid intake and opioid seeking in animal models of opioid reward and reinforcement. The purpose of this study was to examine the effects of ovarian hormones on the discriminative stimulus effects of morphine and naloxone-precipitated opioid withdrawal. To this end, separate groups of ovariectomized female rats were trained to discriminate the stimulus effects of either 3.0 or 10 mg/kg morphine, and substitution tests were conducted with estradiol or progesterone alone and in combination with morphine. At the conclusion of discrimination testing, rats were treated chronically with estradiol, progesterone, or their combination, and challenged with naloxone to measure opioid-like withdrawal symptoms. Finally, the effects of estradiol, progesterone, and their combination were examined on naloxone-precipitated withdrawal in morphine-dependent rats. Neither estradiol nor progesterone substituted for the morphine discriminative stimulus, but estradiol significantly increased the potency of morphine in rats trained to discriminate 10 mg/kg but not 3 mg/kg morphine. When administered chronically, neither hormone nor their combination produced an opioid-like withdrawal syndrome following a naloxone challenge. Acute administration of estradiol, but not progesterone or a combination of estradiol and progesterone, significantly reduced naloxone-precipitated weight loss in morphine-dependent rats. These data indicate that estradiol influences the behavioral effects of morphine, possibly by increasing endogenous tone at mu opioid receptors.
卵巢激素影响内源性阿片类物质的活性，外源性给予雌二醇可减少动物模型中阿片类药物奖赏和强化的阿片类药物摄入和寻求。本研究的目的是研究卵巢激素对吗啡和纳洛酮诱发的阿片类药物戒断的辨别刺激效应的影响。为此，将单独的一组去卵巢雌性大鼠训练为辨别 3.0 或 10mg/kg 吗啡的刺激效应，并用雌二醇或孕酮单独和与吗啡联合进行替代测试。在辨别测试结束时，大鼠接受雌二醇、孕酮或其组合的慢性治疗，并接受纳洛酮挑战以测量类阿片样戒断症状。最后，研究了雌二醇、孕酮及其组合对吗啡依赖大鼠纳洛酮诱发戒断的影响。雌二醇和孕酮均不能替代吗啡的辨别刺激，但雌二醇可显著增加 10mg/kg 而不是 3mg/kg 吗啡训练大鼠的吗啡效力。长期给予时，激素或其组合在纳洛酮挑战后均未产生类阿片样戒断综合征。雌二醇的急性给药，而不是孕酮或雌二醇和孕酮的组合，可显著减少吗啡依赖大鼠纳洛酮诱发的体重减轻。这些数据表明，雌二醇影响吗啡的行为效应，可能通过增加内源性阿片类药物μ受体的张力。
