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Wheel running during chronic nicotine exposure is protective against mecamylamine-precipitated withdrawal and up-regulates hippocampal ?7 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 ?4?2*, ?7 nicotinic acetylcholine (nAChR), ?-opioid (? 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 ?4?2*, ?7 nAChRs, ? 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 ?7 nAChR binding in the CA2/3 area of the hippocampus of nicotine-treated mice. Neither exercise nor nicotine treatment affected ? or D2 receptor binding or BDNF levels. Nicotine withdrawal increased plasma corticosterone levels and ?4?2* nAChR binding, irrespective of exercise regimen. CONCLUSIONS AND IMPLICATIONS:We 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. 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.

SUBMITTER: Keyworth H

PROVIDER: S-EPMC5978981 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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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.

Keyworth Helen H Georgiou Polymnia P Zanos Panos P Rueda André Veloso AV Chen Ying Y Kitchen Ian I Camarini Rosana R Cropley Mark M Bailey Alexis A

British journal of pharmacology 20171222 11

<h4>Background and purpose</h4>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 D<sub>2</sub> dopamine receptors and on brain-derived neurotrophic factor (BDNF) and plasma corticosterone levels ...[more]

PMID: 29266170

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Project description:In two separate experiments, voluntary resistance wheel running with 30% of body weight (RWR), rather than wheel running (WR), led to greater enhancements, including adult hippocampal neurogenesis and cognitive functions, in conjunction with hippocampal brain-derived neurotrophic factor (BDNF) signaling (Lee et al., J Appl Physiol, 2012; Neurosci Lett., 2013). Here we aimed to unravel novel molecular factors and gain insight into underlying molecular mechanisms for RWR-enhanced hippocampal functions; a high-throughput whole-genome DNA microarray approach was applied to rats performing voluntary running for 4 weeks. RWR rats showed a significant decrease in average running distances although average work levels increased immensely, by about 11-fold compared to WR, resulting in muscular adaptation for the fast-twitch plantaris muscle. Global transcriptome profiling analysis identified 128 (sedentary × WR) and 169 (sedentary × RWR) up-regulated (>1.5-fold change), and 97 (sedentary × WR) and 468 (sedentary × RWR) down-regulated (<0.75-fold change) genes. Functional categorization using both pathway- or specific-disease-state-focused gene classifications and Ingenuity Pathway Analysis (IPA) revealed expression pattern changes in the major categories of disease and disorders, molecular functions, and physiological system development and function. Genes specifically regulated with RWR include the newly identified factors of NFATc1, AVPR1A, and FGFR4, as well as previously known factors, BDNF and CREB mRNA. Interestingly, RWR down-regulated multiple inflammatory cytokines (IL1B, IL2RA, and TNF) and chemokines (CXCL1, CXCL10, CCL2, and CCR4) with the SYCP3, PRL genes, which are potentially involved in regulating hippocampal neuroplastic changes. These results provide understanding of the voluntary-RWR-related hippocampal transcriptome, which will open a window to the underlying mechanisms of the positive effects of exercise, with therapeutic value for enhancing hippocampal functions.

Dataset Information

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

Publications

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

Similar Datasets

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