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Wheel running during chronic nicotine exposure is protective against mecamylamine-precipitated withdrawal and up-regulates hippocampal α7 nACh receptors in mice.

Abstract：

BACKGROUND AND PURPOSE:Evidence suggests that exercise decreases nicotine withdrawal symptoms in humans; however, the mechanisms mediating this effect are unclear. We investigated, in a mouse model, the effect of exercise intensity during chronic nicotine exposure on nicotine withdrawal severity, binding of α4β2*, α7 nicotinic acetylcholine (nAChR), μ-opioid (μ receptors) and D2 dopamine receptors and on brain-derived neurotrophic factor (BDNF) and plasma corticosterone levels. EXPERIMENTAL APPROACH:Male C57Bl/6J mice treated with nicotine (minipump, 24 mg·kg-1 ·day-1 ) or saline for 14 days underwent one of three concurrent exercise regimes: 24, 2 or 0 h·day-1 voluntary wheel running. Mecamylamine-precipitated withdrawal symptoms were assessed on day 14. Quantitative autoradiography of α4β2*, α7 nAChRs, μ receptors and D2 receptor binding was performed in brain sections of these mice. Plasma corticosterone and brain BDNF levels were also measured. KEY RESULTS:Nicotine-treated mice undertaking 2 or 24 h·day-1 wheel running displayed a significant reduction in withdrawal symptom severity compared with the sedentary group. Wheel running induced a significant up-regulation of α7 nAChR binding in the CA2/3 area of the hippocampus of nicotine-treated mice. Neither exercise nor nicotine treatment affected μ or D2 receptor binding or BDNF levels. Nicotine withdrawal increased plasma corticosterone levels and α4β2* nAChR binding, irrespective of exercise regimen. CONCLUSIONS AND IMPLICATIONS:We demonstrated for the first time a profound effect of exercise on α7 nAChRs in nicotine-dependent animals, irrespective of exercise intensity. These findings shed light onto the mechanism underlining the protective effect of exercise on the development of nicotine dependence. LINKED ARTICLES:This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Keyworth H,Georgiou P,Zanos P,Rueda AV,Chen Y,Kitchen I,Camarini R,Cropley M,Bailey A

doi

10.1111/bph.14068

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

1928-1943

issue

eissn

0007-1188

issn

1476-5381

journal_volume

175

pub_type

杂志文章

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Wheel running during chronic nicotine exposure is protective against mecamylamine-precipitated withdrawal and up-regulates hippocampal α7 nACh receptors in mice.