Wheel running during chronic nicotine exposure is protective against mecamylamine-precipitated withdrawal and up-regulates hippocampal alpha 7 nACh receptors in mice

Author(s)

Keyworth, Helen ; Georgiou, Polymnia ; Zanos, Panos ; Rueda, Andre Veloso ; Chen, Ying ; Kitchen, Ian ; Camarini, Rosana ; Cropley, Mark ; Bailey, Alexis

• Document type: Journal article
• Source: British Journal of Pharmacology; v. 175, n. 11, p. 16-pg., 2018-06-01.

Abstract

Background and PurposeEvidence 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 42*, 7 nicotinic acetylcholine (nAChR), -opioid ( receptors) and D-2 dopamine receptors and on brain-derived neurotrophic factor (BDNF) and plasma corticosterone levels. Experimental ApproachMale C57Bl/6J mice treated with nicotine (minipump, 24mgkg(-1)day(-1)) or saline for 14days underwent one of three concurrent exercise regimes: 24, 2 or 0hday(-1) voluntary wheel running. Mecamylamine-precipitated withdrawal symptoms were assessed on day 14. Quantitative autoradiography of 42*, 7 nAChRs, receptors and D-2 receptor binding was performed in brain sections of these mice. Plasma corticosterone and brain BDNF levels were also measured. Key ResultsNicotine-treated mice undertaking 2 or 24hday(-1) wheel running displayed a significant reduction in withdrawal symptom severity compared with the sedentary group. Wheel running induced a significant up-regulation of 7 nAChR binding in the CA2/3 area of the hippocampus of nicotine-treated mice. Neither exercise nor nicotine treatment affected or D-2 receptor binding or BDNF levels. Nicotine withdrawal increased plasma corticosterone levels and 42* nAChR binding, irrespective of exercise regimen. Conclusions and ImplicationsWe demonstrated for the first time a profound effect of exercise on 7 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. (AU)

• FAPESP's process: 12/50207-8 - Effects and neurobiological mechanisms of environmental manipulations on ethanol and nicotine induced behavioural effects: involvement of the stress circuitry
• Grantee: Rosana Camarini
• Support Opportunities: Regular Research Grants