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We investigated, in a mouse model, the effect of exercise intensity during chronic nicotine exposure on nicotine withdrawal severity, binding of \u03b14\u03b22*, \u03b17 nicotinic acetylcholine (nAChR), \u03bc\u2010opioid (\u03bc receptors) and D<jats:sub>2<\/jats:sub>dopamine receptors and on brain\u2010derived neurotrophic factor (BDNF) and plasma corticosterone levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Male C57Bl\/6J mice treated with nicotine (minipump, 24\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>) or saline for 14\u00a0days underwent one of three concurrent exercise regimes: 24, 2 or 0\u00a0h\u00b7day<jats:sup>\u22121<\/jats:sup>voluntary wheel running. Mecamylamine\u2010precipitated withdrawal symptoms were assessed on day 14. Quantitative autoradiography of \u03b14\u03b22*, \u03b17 nAChRs, \u03bc receptors and D<jats:sub>2<\/jats:sub>receptor binding was performed in brain sections of these mice. Plasma corticosterone and brain BDNF levels were also measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Nicotine\u2010treated mice undertaking 2 or 24\u00a0h\u00b7day<jats:sup>\u22121<\/jats:sup>wheel running displayed a significant reduction in withdrawal symptom severity compared with the sedentary group. Wheel running induced a significant up\u2010regulation of \u03b17 nAChR binding in the CA2\/3 area of the hippocampus of nicotine\u2010treated mice. Neither exercise nor nicotine treatment affected \u03bc or D<jats:sub>2<\/jats:sub>receptor binding or BDNF levels. Nicotine withdrawal increased plasma corticosterone levels and \u03b14\u03b22* nAChR binding, irrespective of exercise regimen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>We demonstrated for the first time a profound effect of exercise on \u03b17 nAChRs in nicotine\u2010dependent animals, irrespective of exercise intensity. These findings shed light onto the mechanism underlining the protective effect of exercise on the development of nicotine dependence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v175.11\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v175.11\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14068","type":"journal-article","created":{"date-parts":[[2017,12,20]],"date-time":"2017-12-20T05:03:54Z","timestamp":1513746234000},"page":"1928-1943","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Wheel running during chronic nicotine exposure is protective against mecamylamine\u2010precipitated withdrawal and up\u2010regulates hippocampal \u03b17 nACh receptors in mice"],"prefix":"10.1111","volume":"175","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0607-6543","authenticated-orcid":false,"given":"Helen","family":"Keyworth","sequence":"first","affiliation":[{"name":"School of 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