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Wheel running during chronic nicotine exposure is protective against mecamylamine-precipitated withdrawal and upregulates hippocampal a7 nACh receptors in mice

Keyworth, Helen, Georgiou, Polymnia, Zanos, Panos, Veloso Rueda, Andre, Chen, Ying, Kitchen, Ian, Camarini, Rosana, Cropley, Mark and Bailey, Alexis (2017) Wheel running during chronic nicotine exposure is protective against mecamylamine-precipitated withdrawal and upregulates hippocampal a7 nACh receptors in mice British Journal of Pharmacology, 175 (11). pp. 1928-1943.

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Background and purpose. Evidence suggests that exercise decreases nicotine withdrawal symptoms in humans; however, the mechanisms mediating this effect are unclear. We investigate, 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 hrs 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 hrs day-1 wheel running displayed a significant reduction of withdrawal symptom severity compared with the sedentary group. Wheel-running induced a significant upregulation 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 demonstrate for the first time a profound effect of exercise on α7 nAChRs of nicotine-dependent animals, irrespective of exercise intensity. These findings shed light onto the mechanism underlining the protective effect of exercise in the development of nicotine dependence.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Psychology
Authors :
Keyworth, Helen
Georgiou, Polymnia
Zanos, Panos
Veloso Rueda, Andre
Chen, Ying
Camarini, Rosana
Date : 22 December 2017
Identification Number : 10.1111/bph.14068
Copyright Disclaimer : © 2017 The British Pharmacological Society
Uncontrolled Keywords : Chronic nicotine; Withdrawal; Exercise; α7 nicotinic receptors; Hippocampus
Depositing User : Clive Harris
Date Deposited : 26 Sep 2017 10:35
Last Modified : 26 Jun 2018 12:27

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