Regulation of α4β2α5 nicotinic acetylcholinergic receptors in rat cerebral cortex in early and late adolescence: Sex differences in response to chronic nicotine.
Regulation of α4β2α5 nicotinic acetylcholinergic receptors in rat cerebral cortex in early and late adolescence: Sex differences in response to chronic nicotine.
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DOI：
10.1016/j.neuropharm.2015.08.015
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发表时间：
2015-12
影响因子：
4.7
通讯作者：
Perry DC
中科院分区：
文献类型：
--
作者：
Hoegberg BG;Lomazzo E;Lee NH;Perry DC
在动物中长期给予尼古丁和在人类中吸烟会导致α4β2* 神经元烟碱受体（nAChR）的上调，这被假设有助于尼古丁的成瘾作用。我们使用大鼠模型来测试这种上调效应在青少年与成年人以及男性与女性中是否存在差异。通过皮下渗透微型泵给予尼古丁或生理盐水长期治疗后，我们使用[3H]地棘蛙素标记组装的nAChR，并使用选择性抗体通过免疫沉淀法测量单个亚基，从而测量大脑皮层中的α4β2和α4β2α5 nAChR。我们首次详细描述了雌性青春期大鼠大脑皮层中α4β2和α4β2α5 nAChR的反应。我们发现尼古丁诱导的上调在青春期早期的男性和女性之间的差异，在青春期后期和成年期都没有。雄性在PN28时显示出显著上调，而在年龄匹配的雌性中不存在。这些结果表明，基于年龄，大脑皮层中α4β2* nAChR对慢性尼古丁暴露影响的敏感性存在性别差异。
Chronic nicotine administration in animals, and smoking in humans, causes up-regulation of α4β2* neuronal nicotinic receptors (nAChRs), which has been hypothesized to contribute to the addictive actions of nicotine. We used a rat model to test whether such up-regulatory effects differ in adolescents versus adults, and in males versus females. Following chronic treatment with nicotine or saline via subcutaneous osmotic minipumps, we measured α4β2 and α4β2α5 nAChRs in cerebral cortex using [3H]epibatidine to label assembled nAChRs, and selective antibodies to measure the individual subunits via immunoprecipitation. For the first time, we provide a detailed characterization of the response of both α4β2 and α4β2α5 nAChRs in female adolescent rat cerebral cortex. We found differences in nicotine-induced up-regulation between males and females in early adolescence that are absent in both late adolescence and adulthood. Males showed significant up-regulation at PN28 which was absent in age-matched females. These results demonstrate sex differences in the susceptibility of α4β2* nAChRs to the effects of chronic nicotine exposure in the cerebral cortex based on age.