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.

• Authors: Helen Keyworth, Polymnia Georgiou, Panos Zanos, André Veloso Rueda, Ying Chen, Ian Kitchen, Rosana Camarini, Mark Cropley, Alexis Bailey
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 175 Issue 11 Pg. 1928-1943 (06 2018) ISSN: 1476-5381 [Electronic] England
• PMID: 29266170 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 The British Pharmacological Society.

Chemical References

• Protective Agents
• alpha7 Nicotinic Acetylcholine Receptor
• Mecamylamine
• Nicotine

Topics

• Animals
• Male
• Mecamylamine (antagonists & inhibitors, pharmacology)
• Mice
• Mice, Inbred C57BL
• Nicotine (administration & dosage, pharmacology)
• Protective Agents (administration & dosage, pharmacology)
• Up-Regulation (drug effects)
• alpha7 Nicotinic Acetylcholine Receptor (antagonists & inhibitors, metabolism)