Sex differences in cholinergic systems in the interpeduncular nucleus following nicotine exposure and withdrawal
Sex differences in cholinergic systems in the interpeduncular nucleus following nicotine exposure and withdrawal
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DOI：
10.1016/j.neuropharm.2019.107714
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发表时间：
2019-11-01
影响因子：
4.7
通讯作者：
O'Dell, Laura E.
中科院分区：
文献类型：
--
作者：
Correa, Victor L.;Flores, Rodolfo J.;O'Dell, Laura E.
内侧缰核-脚间核（MHb-IPN）通路调节尼古丁戒断产生的负性情感状态。尚未探讨乙酰胆碱（ACh）系统在这一途径中的作用的性别差异。因此，本研究评估了乙酰胆碱水平和基因表达的α-和β-含烟碱乙酰胆碱受体（nAChR）亚基在IPN的雌性和雄性大鼠尼古丁治疗和戒断后。大鼠用泵输送尼古丁14天，而未处理的对照组接受假手术。在研究1中，大鼠在IPN中准备了探针，并在生理盐水和美加明给药后测量ACh水平。在研究2中，单独的未处理对照组或尼古丁处理组大鼠接受生理盐水或美加明，并使用高架十字迷宫（高架十字迷宫）程序评估体征和焦虑样行为。然后解剖IPN并使用RT-qPCR方法评估mRNA水平。尼古丁治疗增加乙酰胆碱水平在更大程度上在女性比男性。尼古丁戒断产生了相似的体征增加;然而，女性比男性表现出更大的焦虑样行为。在雌性中，α 5的基因表达在尼古丁处理和戒断后增加。在雄性动物中，尼古丁给药后α 7升高，尼古丁戒断期间α 2和α 3升高。在尼古丁戒断期间，雌性和雄性的β 3和β 4均显示增加。在女性中，焦虑样行为与IPN中的α 4、α 5和β 2基因表达相关。这些结果表明，撤回的性别差异调制通过胆碱能系统的IPN。
The medial habenula-interpeduncular nucleus (MHb-IPN) pathway modulates negative affective states produced by nicotine withdrawal. Sex differences in the contribution of acetylcholine (ACh) systems in this pathway have not been explored. Thus, this study assessed ACh levels and gene expression of alpha- and beta-containing nicotinic acetylcholine receptor (nAChR) subunits in the IPN of female and male rats following nicotine treatment and withdrawal. Rats were prepared with a pump that delivered nicotine for 14 days, and naive controls received a sham surgery. In Study 1, rats were prepared with a probe in the IPN, and ACh levels were measured following saline and then mecamylamine administration. In Study 2, separate groups of naive control or nicotine-treated rats received saline or mecamylamine and physical signs and anxiety-like behavior were assessed using elevated plus maze (EPM) procedures. The IPN was then dissected and mRNA levels were assessed using RT-qPCR methods. Nicotine treatment increased ACh levels to a larger extent in females than males. Nicotine withdrawal produced a similar increase in physical signs; however, females displayed greater anxiety-like behavior than males. In females, gene expression of alpha 5 increased following nicotine treatment and withdrawal. In males, alpha 7 increased following nicotine treatment and alpha 2 and alpha 3 increased during nicotine withdrawal. Both females and males displayed an increase in beta 3 and beta 4 during nicotine withdrawal. In females, anxiety-like behavior was correlated with alpha 4, alpha 5, and beta 2 gene expression in the IPN. These results suggest that sex differences in withdrawal are modulated via cholinergic systems in the IPN.