Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA.
Drug Alcohol Depend. 2023 Nov 1;252:110983. doi: 10.1016/j.drugalcdep.2023.110983. Epub 2023 Sep 27.
Rates of tobacco and alcohol use in women are rising, and women are more vulnerable than men to escalating tobacco and alcohol use. Many women use hormonal birth control, with the oral contraceptive pill being the most prevalent. Oral contraceptives contain both a progestin (synthetic progesterone) and a synthetic estrogen (ethinyl estradiol; EE) and are contraindicated for women over 35 years who smoke. Despite this, no studies have examined how synthetic contraceptive hormones impact this pattern of polysubstance use in females. To address this critical gap in the field, we treated ovary-intact female rats with either sesame oil (vehicle), the progestin levonorgestrel (LEVO; contained in formulations such as Alesse®), or the combination of EE+LEVO in addition to either undergoing single (nicotine or saline) or polydrug (nicotine and ethanol; EtOH) self-administration (SA) in a sequential use model. Rats preferred EtOH over water following extended EtOH drinking experience as well as after nicotine or saline SA experience, and rats undergoing only nicotine SA (water controls) consumed more nicotine as compared to rats co-using EtOH and nicotine. Importantly, this effect was occluded in groups treated with contraceptive hormones. In the sequential use group, both LEVO alone and the EE+LEVO combination occluded the ability of nicotine to decrease EtOH consumption. Interestingly, demand experiments suggest an economic substitute effect between nicotine and EtOH. Together, we show that chronic synthetic hormone exposure impacts nicotine and EtOH sequential use, demonstrating the crucial need to understand how chronic use of different contraceptive formulations alter patterns of polydrug use in women.
女性的烟草和酒精使用率正在上升，而且女性比男性更容易受到烟草和酒精使用增加的影响。许多女性使用激素避孕方法，其中最常见的是口服避孕药。口服避孕药含有孕激素（合成黄体酮）和合成雌激素（炔雌醇；EE），不适合 35 岁以上吸烟的女性。尽管如此，没有研究检查过合成避孕药中的激素如何影响女性这种多物质使用模式。为了解决该领域的这一关键差距，我们用芝麻油（载体）、孕激素左炔诺孕酮（LEVO；包含在 Alesse®等配方中）或 EE+LEVO 的组合治疗卵巢完整的雌性大鼠，以及接受单一（尼古丁或生理盐水）或多药物（尼古丁和乙醇；EtOH）自我给药（SA）在顺序使用模型中。在延长的 EtOH 饮酒经历后，以及在尼古丁或生理盐水 SA 经历后，大鼠更喜欢 EtOH 而不是水，并且仅接受尼古丁 SA（水对照）的大鼠消耗的尼古丁比同时使用 EtOH 和尼古丁的大鼠多。重要的是，这种作用在接受避孕药激素治疗的组中被阻断。在顺序使用组中，LEVO 单独和 EE+LEVO 组合阻断了尼古丁降低 EtOH 消耗的能力。有趣的是，需求实验表明尼古丁和 EtOH 之间存在经济替代效应。总之，我们表明慢性合成激素暴露会影响尼古丁和 EtOH 的顺序使用，这表明迫切需要了解不同避孕药配方的慢性使用如何改变女性多药物使用模式。
