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雄性和雌性大鼠在 Y 迷宫范式中表现出阿片类药物戒断引起的位置厌恶和消退。

Male and female rats show opiate withdrawal-induced place aversion and extinction in a Y-maze paradigm.

机构信息

Univ. Bordeaux, CNRS, INCIA, UMR 5287, F-33000 Bordeaux, France.

Univ. Bordeaux, CNRS, INCIA, UMR 5287, F-33000 Bordeaux, France.

出版信息

Behav Brain Res. 2023 Feb 2;437:114122. doi: 10.1016/j.bbr.2022.114122. Epub 2022 Sep 26.

DOI:10.1016/j.bbr.2022.114122
PMID:36174840
Abstract

Gender differences have been observed in the vulnerability to drug abuse and in the different stages of the addictive process. In opiate dependence, differences between sexes have been shown in humans and laboratory animals in various phases of opiate addiction, especially in withdrawal-associated negative affective states. Using a Y-maze conditioned place aversion paradigm, we investigated potential sex differences in the expression and extinction of the aversive memory of precipitated opiate withdrawal state in morphine-dependent rats. No significant difference between sexes was observed in the occurrence of withdrawal signs following naloxone injection during conditioning. Moreover, opiate withdrawal memory expression and extinction following repeated testing was demonstrated in both male and female rats, with no significant differences between sexes. Finally, we report spontaneous recovery following extinction of opiate withdrawal memory. Altogether these data provide further evidence that persistent withdrawal-related memories may be strong drivers of opiate dependence, and demonstrate that both males and females can be used in experimental rodent cohorts to better understand opiate-related effects, reward, aversive state of withdrawal, abstinence and relapse.

摘要

性别差异在滥用药物的易感性和成瘾过程的不同阶段都有体现。在阿片类药物依赖中,人类和实验室动物在阿片类药物成瘾的各个阶段都表现出了性别差异,特别是在戒断相关的消极情绪状态中。本研究使用 Y 型迷宫条件性位置厌恶范式,研究了在吗啡依赖大鼠中,预先引起的阿片类药物戒断状态的厌恶记忆表达和消退过程中,潜在的性别差异。在条件作用期间注射纳洛酮后,男女两性出现戒断体征的情况没有显著差异。此外,雄性和雌性大鼠在重复测试后均表现出阿片类戒断记忆的表达和消退,两性之间没有显著差异。最后,我们报告了阿片类戒断记忆消退后的自发恢复。总之,这些数据进一步证明了持续的戒断相关记忆可能是阿片类药物依赖的主要驱动力,并表明雄性和雌性大鼠都可以用于实验性啮齿动物队列,以更好地了解与阿片类药物相关的效应、奖励、戒断的厌恶状态、禁欲和复发。

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