Contraceptive hormone ethinyl estradiol but not levonorgestrel modulates the role of reinforcer-enhancement in nicotine self-administration in ovary-intact female Sprague-Dawley rats

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2025-09-08 DOI:10.1016/j.neuropharm.2025.110681

Kathleen R. McNealy , MacKenzie L. Knabel , Scott T. Barrett , Cassandra D. Gipson , Tierney K. Lorenz , Rick A. Bevins

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Abstract

Hormonal contraceptives containing a synthetic estrogen (e.g., ethinyl estradiol/EE) and/or a progestin (e.g., levonorgestrel/LEVO) are associated with heightened nicotine use. Whether altered intake reflects changes in nicotine reinforcement or nicotine enhancement of co-occurring reinforcers is unknown. Reinforcer-enhancement is evidenced when nicotine self-administration increases when delivered with a reinforcing visual stimulus (VS). We examined EE and LEVO effects on nicotine reinforcement and reinforcer-enhancement in ovary-intact female Sprague-Dawley rats. Rats were implanted with a jugular catheter and received daily EE (Vehicle, 0.125 [Low], or 0.18 [High] μg/day; Experiment 1 N = 95) or LEVO (Vehicle, 0.3 [Low], or 0.6 [High] μg/day; Experiment 2 N = 113) injections. Rats responded for saline, 0.03 or 0.06 mg/kg/inf nicotine during two phases: the Infusion Only phase, responding only for their assigned solution, and the Infusion + VS phase, responding for their assigned solution and a VS. Each phase consisted of two Fixed Ratio-1 and ten Variable Ratio-3 sessions. The Infusion + VS phase included five additional Progressive Ratio sessions. In both experiments, only 0.06 mg/kg/inf nicotine maintained self-administration during the Infusion Only phase. This self-administration was unchanged by EE or LEVO. Nicotine self-administration increased during the Infusion + VS phase. In Experiment 1, 0.03 mg/kg/inf nicotine self-administration decreased with increasing EE dose; 0.06 mg/kg/inf nicotine self-administration was unchanged. For Experiment 2, LEVO did not alter self-administration. EE and LEVO were physiologically effective, evidenced by disrupted estrous cycling and EE increasing uterine weights. EE but not LEVO altered nicotine reinforcer-enhancement. These findings suggest a potential behavioral mechanism by which hormonal contraceptives alter nicotine intake in women.

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避孕激素炔雌醇而非左炔诺孕酮调节卵巢完整雌性sd - dawley大鼠尼古丁自我给药中的强化物增强作用。

含有合成雌激素（如乙炔雌二醇/EE）和/或黄体酮（如左炔诺孕酮/左炔诺孕酮）的激素避孕药与尼古丁使用量增加有关。摄入量的改变是否反映了尼古丁强化的变化或尼古丁对共同发生的强化物的增强尚不清楚。强化物增强被证明当尼古丁自我给药增加时，提供强化视觉刺激（VS）。我们研究了EE和LEVO对卵巢完好的雌性Sprague-Dawley大鼠尼古丁强化和强化物增强的影响。大鼠植入颈静脉导管，每日接受EE （Vehicle， 0.125 [Low]或0.18 [High] μg/d；实验1 N=95）或LEVO （Vehicle， 0.3 [Low]或0.6 [High] μg/d；实验2 N=113）注射。大鼠对生理盐水、0.03或0.06 mg/kg/inf尼古丁有反应分为两个阶段：只对指定溶液有反应的输注阶段，和对指定溶液和VS有反应的输注+VS阶段，每个阶段包括两个固定比率1和十个可变比率3阶段。输液+VS阶段包括5个额外的渐进比率阶段。在两个实验中，只有0.06 mg/kg/inf尼古丁在输注阶段维持自我给药。EE或LEVO没有改变这种自我给药。在输注+VS期，尼古丁自我给药量增加。实验1 0.03 mg/kg/inf尼古丁自给药量随EE剂量的增加而减少；0.06 mg/kg/inf尼古丁自我给药不变。在实验2中，LEVO没有改变自我给药。EE和LEVO在生理上是有效的，可以通过扰乱发情周期和EE增加子宫重量来证明。EE而不是LEVO改变了尼古丁强化剂的增强作用。这些发现表明，激素避孕药改变女性尼古丁摄入量的潜在行为机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).