Background and purpose:
There is substantial evidence to suggest that exercise decreases nicotine withdrawal symptoms in humans; however, the mechanism mediating this effect is unclear. Here we investigate in a mouse model the effect of exercise intensity on nicotine withdrawal symptom severity and the binding of α4β2*, α7 nicotinic acetylcholine (nAChR), μ-opioid (MOPr) 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/day) 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, MOPr and D2 receptor binding was performed in brain sections of these mice. Corticosterone and BDNF levels were measured in plasma and brain regions, respectively.

Key results:
Male C57Bl/6J mice treated with nicotine (minipump, 24 mg/kg/day) 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, MOPr and D2 receptor binding was performed in brain sections of these mice. Corticosterone and BDNF levels were measured in plasma and brain regions, respectively.

Conclusions and implications:
. Exercise reduces nicotine withdrawal symptoms irrespective of intensity. This is concomitant with an upregulation of α7 nAChRs in the hippocampus. This novel mechanism may underline the beneficial effect of exercise on nicotine withdrawal.