Adult and periadolescent rats differ in expression of nicotinic cholinergic receptor subtypes and in the response of these subtypes to chronic nicotine exposure
Adult and periadolescent rats differ in expression of nicotinic cholinergic receptor subtypes and in the response of these subtypes to chronic nicotine exposure
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DOI：
10.1016/j.brainres.2008.03.056
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发表时间：
2008-06-18
期刊：
影响因子：
2.9
通讯作者：
Perry, David C.
中科院分区：
文献类型：
--
作者：
Doura, Menahem B.;Gold, Allison B.;Perry, David C.
青春期是大脑发育的重要时期，在此期间暴露于尼古丁与随后较高的依赖率有关。慢性尼古丁暴露会改变烟碱乙酰胆碱受体（nAChR）的表达，从而改变尼古丁反应模式。我们使用定量放射自显影法测量成年和青春期大鼠慢性尼古丁暴露后渗透微型泵的nAChRs的三个主要亚型。两个不同年龄的对照动物的比较显示，与成年人的相同大脑区域相比，青少年前期表达的α 4 β 2* nAChR的数量始终更大。与成年大鼠相比，在对照的青春期大鼠中发现了α 7 nAChR类似但不太明显的增加。成人和青少年之间[I-121] α-芋螺毒素MII（主要与α 6* nAChR）的结合没有系统性差异。对慢性尼古丁暴露的反应也因年龄而异。在成年动物中，α 4 β 4* nAChRs的上调是突出和广泛的;在青春期，α 4 β 2* 上调也发生了，但在较少的区域和较小的程度。α 7受体也有类似的反应模式：成人对尼古丁诱导的上调反应比青少年期更敏感。在成年动物中，慢性尼古丁暴露不会引起α 6* nAChRs的上调;在三个区域中结合下调。与其他亚型不同，α 6* nAChRs对慢性尼古丁的反应在青春期更大，与成人相比，更多的区域显示出更大的下调。考虑到青少年对尼古丁诱导的行为变化的独特脆弱性和对药物滥用的易感性，年龄组之间受体表达和调节的这些差异可能是重要的。(c)2008 Elsevier B. V.保留所有权利。
Adolescence is a time of significant brain development, and exposure to nicotine during this period is associated with higher subsequent rates of dependence. Chronic nicotine exposure alters expression of nicotinic acetylcholine receptors (nAChRs), changing the pattern of nicotine responsiveness. We used quantitative autoradiography to measure three major subtypes of nAChRs after chronic nicotine exposure by osmotic minipump in adult and periadolescent rats. Comparison of control animals at the two different ages revealed that periadolescents express consistently greater numbers of alpha 4 beta 2* nAChRs compared to the same brain regions of adults. Similar but less pronounced increases in alpha 7 nAChRs were found in control periadolescent rats compared to adults. Binding of [I-121]alpha-conotoxin MII (largely to alpha 6* nAChRs) did not systematically differ between adults and periadolescents. The response to chronic nicotine exposure also differed by age. Up-regulation of alpha 4 beta 4* nAChRs was prominent and widespread in adult animals; in periadolescents, alpha 4 beta 2* up-regulation also occurred, but in fewer regions and to a lesser extent. A similar pattern of response was seen with alpha 7 receptors: adults were more responsive than periadolescents to nicotine-induced up-regulation. In adult animals, chronic nicotine exposure did not cause up-regulation of alpha 6* nAChRs; binding was down-regulated in three regions. Unlike the other subtypes, the response of alpha 6* nAChRs to chronic nicotine was greater in periadolescents, with more regions showing greater down-regulation compared to adults. These differences in receptor expression and regulation between age groups are likely to be important given the unique vulnerability of adolescents to nicotine-induced behavioral changes and susceptibility to drug abuse. (c) 2008 Elsevier B.V. All rights reserved.