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Brain Sci. 2018, 8(4), 70;

Sex Specific Alterations in α4*Nicotinic Receptor Expression in the Nucleus Accumbens

Institute of Health and Medical Innovation, Queensland University of Technology, Translational Research Institute, 37 Kent St, Woolloongabba, QLD 4102, Australia
Author to whom correspondence should be addressed.
Received: 28 February 2018 / Revised: 12 April 2018 / Accepted: 16 April 2018 / Published: 19 April 2018
(This article belongs to the Special Issue Sex Differences in the Healthy and Diseased Brain)
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Background: The mechanisms leading from traumatic stress to social, emotional and cognitive impairment and the development of mental illnesses are still undetermined and consequently there remains a critical need to develop therapies for preventing the adverse consequences of traumatic stress. Research indicates nicotinic acetylcholine receptors containing α4 subunits (α4*nAChRs) are both impacted by stress and capable of modulating the stress response. In this study, we investigated whether varenicline, a partial α4β2*nAChR agonist which reduces nicotine, alcohol and sucrose consumption, can reduce stress, a driving factor in substance use disorders. We also examined the effect of stress on nucleus accumbens (NAc) α4*nAChR expression. Methods: Transgenic mice with fluorescent tags attached to α4*nAChRs were administered varenicline and/or yohimbine (a pharmacological stressor) and plasma corticosterone and NAc α4*nAChR expression were measured. A separated group of mice were exposed to maternal separation (MS) during post-natal day (P) 2–14, then restraint stressed (30 min) at six weeks of age. Body weight, anxiety-like behaviours (elevated plus maze), plasma corticosterone and NAc α4*nAChR levels were measured. Results: Varenicline attenuated yohimbine-induced plasma corticosterone increases with no effect on NAc α4*nAChR expression. MS reduced unrestrained plasma corticosterone levels in both sexes. In females, MS increased body weight and NAc α4*nAChR expression, whereas, in males, MS and restraint caused a greater change in anxiety-like behaviours and plasma corticosterone levels. Restraint altered NAc α4*nAChR expression in both male and female MS mice. Conclusions: The effects of stress on NAc α4*nAChR are sex-dependent. While varenicline attenuated acute stress-induced rises in corticosterone levels, future studies are required to determine whether varenicline is effective for relieving the effects of stress. View Full-Text
Keywords: nicotinic receptors; nucleus accumbens; stress; varenicline; maternal separation nicotinic receptors; nucleus accumbens; stress; varenicline; maternal separation

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Holgate, J.Y.; Tarren, J.R.; Bartlett, S.E. Sex Specific Alterations in α4*Nicotinic Receptor Expression in the Nucleus Accumbens. Brain Sci. 2018, 8, 70.

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