Attenuation of cocaine-seeking by progesterone treatment in female rats
Attenuation of cocaine-seeking by progesterone treatment in female rats
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DOI：
10.1016/j.psyneuen.2008.09.014
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发表时间：
2009-04-01
影响因子：
3.7
通讯作者：
See, Ronald E.
中科院分区：
文献类型：
--
作者：
Feltenstein, Matthew W.;Byrd, Elizabeth A.;See, Ronald E.
临床研究表明，可卡因依赖存在性别差异。同样，临床前研究表明，雌性大鼠在可卡因自我给药、早期灭绝和可卡因诱导的恢复药物寻找过程中表现出更高的反应率。这些影响也是发情周期依赖的，并且与血浆孕酮呈负相关，因为发情前期的雌性(高孕酮)表现出较少的可卡因寻求，而发情雌性(低孕酮)表现出最大的可卡因寻求。基于这些发现，我们假设黄体酮将减弱完整的、自由骑自行车的动物的可卡因寻求行为。在早期(首次获得日)和后期(最后一次维持日)，发情周期对可卡因寻求行为的作用也被检测。雌性Spraogue-Dawley大鼠按照FR1程序自我注射可卡因(0.5 mg/kg/次，iv)，然后在没有可卡因强化的情况下每天戒毒。一旦反应消失，大鼠在恢复测试之前立即注射可卡因(10 mg/kg，ip)。黄体酮(2 mg/kg，SC)或赋形剂在戒断第一天(早期戒断可卡因)和恢复试验前20和2小时给药。为了确定发情周期阶段，我们在第一次获得可卡因和最后一次自我给药、第一天绝育训练和每次恢复试验之前评估了阴道细胞学。在吸食可卡因的早期和晚期，发情前期和发情期的雌性动物分别表现出最高水平的主动水平反应。与非发情期相比，在可卡因刺激的恢复过程中，发情期和非发情期女性的反应也显著增加，这种影响被黄体酮选择性地减弱。然而，在发情周期的其他阶段，黄体酮不能有效地减少可卡因诱导的雌性性欲的恢复，也不能有效地减少在早期戒断过程中的可卡因寻找。综上所述，这些结果表明，黄体酮可能是一种有效的治疗方法，可以预防戒除女性可卡因使用者的复发，特别是在复发可能性最大的情况下。(C)2008爱思唯尔有限公司。保留所有权利。
Clinical research suggests that gender differences exist in cocaine dependence. Similarly, preclinical studies have shown that female rats exhibit higher response rates during cocaine self-administration, early extinction, and cocaine-primed reinstatement of drug-seeking. These effects are also estrous cycle dependent and inversely related to plasma progesterone, in that proestrus females (high progesterone) exhibit less cocaine-seeking, while estrous females (low progesterone) show the greatest cocaine-seeking. Based on these findings, we hypothesized that progesterone would attenuate cocaine-seeking behavior in intact, freely cycling animals. The role of the estrous cycle on cocaine-seeking behavior during early (first acquisition day) versus late (last maintenance day) cocaine self-administration was also examined. Female, Sprague-Dawley rats self-administered cocaine (0.5 mg/kg/infusion, IV) along a FR1 schedule, followed by daily extinction sessions in the absence of cocaine reinforcement. Once responding was extinguished, rats received an injection of cocaine (10 mg/kg, IP) immediately prior to reinstatement testing. Progesterone (2 mg/kg, SC) or vehicle was administered 20 and 2 h prior to the first day of extinction (early cocaine withdrawal) and the reinstatement trials. To determine estrous cycle phase, we assessed vaginal cytology prior to the first acquisition and last maintenance days of cocaine self-administration, the first day of extinction training, and each reinstatement test. During early and late cocaine self-administration, proestrus and estrous females exhibited the greatest levels of active lever responding, respectively. A significant increase in responding also occurred during cocaine-primed reinstatement for estrous versus nonestrous females, an effect that was selectively attenuated by progesterone. However, progesterone was not effective at reducing cocaine-primed reinstatement for females in other phases of the estrous cycle, nor was it effective at reducing cocaine-seeking during early withdrawal. Taken together, these results suggest that progesterone may be a useful therapeutic for preventing relapse in abstinent female cocaine users, especially when the likelihood of relapse is greatest. (C) 2008 Elsevier Ltd. All rights reserved.