期刊
BRAIN RESEARCH
卷 1215, 期 -, 页码 40-52出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2008.03.056
关键词
nicotine; adolescence; dependence; nicotinic receptor subtypes; autoradiography
资金
- NIDA NIH HHS [R01 DA015767-04, R01 DA015767, DA015767] Funding Source: Medline
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.
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