Sex differences in the expression of morphine withdrawal symptoms and associated activity in the tail of the ventral tegmental area
Sex differences in the expression of morphine withdrawal symptoms and associated activity in the tail of the ventral tegmental area
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DOI：
10.1016/j.neulet.2019.04.057
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发表时间：
2019-07-13
影响因子：
2.5
通讯作者：
Perrotti, Linda I.
中科院分区：
文献类型：
--
作者：
Bobzean, Samara A. M.;Kokane, Saurabh S.;Perrotti, Linda I.
最近的研究，在雄性啮齿动物，已经开始阐明的作用，在尾部的腹侧被盖区（tVTA）的GABA能神经元在吗啡戒断。迄今为止，吗啡戒断的机制几乎完全是在雄性动物中研究的。因此，有一个相当大的差距，我们目前的理解的过程中的性别差异，吗啡戒断行为及其对细胞活性的影响，在tVTA的女性。本研究的目的是研究性别对自发性躯体吗啡戒断综合征的表达和持续时间的影响，并描述自发性躯体戒断症状与雄性和雌性大鼠GABA能tVTA中细胞活化（测量为磷酸化CREB; pCREB）之间的关系。吗啡依赖的成年雄性和雌性Long Evans大鼠进行72小时的自发戒断，每12小时评估一次躯体戒断症状。与雌性大鼠相比，雄性吗啡依赖大鼠在戒断的早期阶段表现出更严重的症状。虽然，女性表现出较低的整体症状严重程度，他们的症状持续时间较长，因此表现出较高的戒断症状的严重程度比男性在晚期戒断。吗啡戒断大鼠tVTA中的pCREB活性升高，并且与戒断症状的严重程度呈正相关。这些结果表明，性别差异的表达的时间躯体撤退。我们的数据增加了越来越多的证据，证明tVTA在吗啡戒断中的作用，并开始在该大脑区域内建立性别依赖性行为和分子特征。
Recent studies, in male rodents, have begun to elucidate a role for the GABAergic neurons in the tail of the ventral tegmental area (tVTA) in morphine withdrawal. To date, the mechanisms underlying morphine withdrawal have been studied almost exclusively in male animals. As a result, there is a considerable gap in our current understanding of the processes underlying sex differences in morphine withdrawal behaviors and its effects on cellular activity in the tVTA in females. The purpose of the present study was to investigate the influence of sex on the expression and duration of spontaneous somatic morphine withdrawal syndrome, and to characterize the relationship between spontaneous somatic withdrawal symptoms and cellular activation (measured as phosphorylated CREB; pCREB), in the GABAergic tVTA in male and female rats. Morphine-dependent adult male and female Long Evans rats underwent 72 h of spontaneous withdrawal, and somatic withdrawal symptoms were assessed every 12 h. Male morphine-dependent rats expressed more severe symptoms during the early phases of withdrawal compared to females. Although, females demonstrated lower overall symptom severity, their symptoms persisted for a longer period of time, thus demonstrating higher withdrawal-symptom severity than males during late withdrawal. pCREB activity in the tVTA was elevated in morphine-withdrawn rats and was positively correlated with the severity of withdrawal symptoms. These results demonstrate sex differences in the timing of the expression of somatic withdrawal. Our data add to the growing body of evidence demonstrating a role for the tVTA in morphine withdrawal and begin to establish a sex-dependent behavioral and molecular profile within this brain region.