Classically, it has been thought that high-affinity nicotinic receptors-containing beta2 subunits are the most important receptor subtypes for nicotinic involvement in cognitive function and nicotine self-administration, while low affinity alpha7-containing nicotinic receptors have not been thought to be important. In the current study, we found that knockout of either beta2 or alpha7 subunits caused significant deficits in spatial discrimination in mice. The character of the impairment in the two knockouts was different. The beta2 knockout preferentially impaired cognition in males while the alpha7 caused impairment regardless of sex. Both beta2- and alpha7-containing nicotinic receptors also are important for nicotine self-administration, also in different ways. Most animal model studies of nicotine self-administration are relatively short-term whereas the problem of tobacco addiction is considerably longer-term. To better model the impact of nicotinic receptor subtypes on nicotine self-administration over the long-term, we studied the impact of genetic knockout of low affinity alpha7 receptors vs. high-affinity beta2-containing nicotinic receptors. Mice with knockouts of either of these receptors and their wildtype counter parts were given free access to a choice of nicotine-containing and nicotine-free solution in their home cages on a continuous basis over a period of 5 months. During the first few weeks, the beta2-containing nicotinic receptor knockout mice showed a significant decrease in nicotine consumption relative to wildtype mice, whereas the alpha7 knockout mice did not significantly differ from wildtype controls at the beginning of their access to nicotine. Interestingly, in the longer-term after the first few weeks of nicotine access, the beta2 knockout mice returned to wildtype mouse levels of nicotine consumption, whereas the alpha7 knockout mice developed an emergent decrease in nicotine consumption. The alpha7 receptor knockout-induced decrease in nicotine consumption persisted for the 5-month period of the study. Both alpha7- and beta2-containing nicotinic receptors play critical roles in cognitive function and nicotine self-administration. Regarding cognitive function, beta2-containing receptors are important for maintaining normal sex differences in spatial learning and memory, whereas alpha7 receptors are important for cognitive function regardless of sex. Regarding nicotine self-administration high-affinity beta2-containing nicotinic receptors are important for consumption during the initial phase of nicotine access, but it is the alpha7 nicotinic receptors that are important for the longer-term regulation of nicotine consumption.

译文

:通常,人们一直认为,含有高亲和力烟碱受体的β2亚基是烟碱参与认知功能和尼古丁自我给药的最重要的受体亚型,而低亲和力的含α7烟碱受体尚未被认为是重要的。在当前的研究中,我们发现敲除beta2或alpha7亚基会导致小鼠的空间分辨力明显不足。两种基因敲除的损伤特征是不同的。 beta2基因敲除优先削弱男性的认知能力,而alpha7则不论性别如何均引起损害。含β2和α7的烟碱样受体对于尼古丁的自我给药也很重要,也有不同的用法。尼古丁自我管理的大多数动物模型研究都是相对短期的,而烟草成瘾的问题则是相当长期的。为了更好地模拟烟碱样受体亚型对尼古丁自我给药的长期影响,我们研究了基因敲除低亲和力α7受体与高亲和力的含β2烟碱样受体的影响。敲除这些受体及其野生型对应部分中的任一个的小鼠可在其笼子中连续5个月自由接触选择的含尼古丁和不含尼古丁的溶液。在最初的几周内,相对于野生型小鼠,含β2的烟碱样受体敲除小鼠的尼古丁消耗量显着减少,而α7敲除小鼠在接触尼古丁的初期与野生型对照无显着差异。有趣的是,在进入尼古丁的最初几周后,长期而言,β2敲除小鼠恢复了野生型小鼠的尼古丁消耗水平,而alpha7敲除小鼠出现了尼古丁消耗的突然下降。在研究的5个月中,α7受体基因敲除引起的尼古丁消耗减少一直持续。含α7和β2的烟碱样受体在认知功能和尼古丁自我给药中都起着关键作用。关于认知功能,含β2受体对于维持空间学习和记忆中的正常性别差异很重要,而alpha7受体对于无论性别如何的认知功能都很重要。关于尼古丁的自我给药,含高亲和力的含β2的尼古丁受体对于尼古丁进入初期的消耗很重要,但是α7尼古丁受体对于长期调节尼古丁的消耗很重要。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录