Behavior and Hippocampal Epac Signaling to Nicotine CPP in Mice.

Jing Liu,Xinrong Tao,Bing Li,Yuting Hu,Song Xue,Qi Wang,Rongbo Zhang,Fei Liu

doi:10.1515/tnsci-2019-0041

Abstract

Tobacco use is a major challenge to public health in the United States and across the world. Many studies have demonstrated that adult men and women differ in their responses to tobacco smoking, however neurobiological studies about the effect of smoking on males and females were limited. Exchange protein directly activated by cAMP (Epac) signaling participates in drug addictive behaviors. In this study, we examined the hippocampal Epac signaling in nicotine-induced place conditioning mice. Nicotine at 0.2 mg/kg and 0.4 mg/kg induced a conditioned place preference (CPP) in male and female mice, respectively. After CPP, male mice presented less anxiety-like behavior as demonstrated by an open-field test. The hippocampal Epac2 protein was elevated in both male and female nicotine place conditioning mice. However, Rap1 protein was elevated and CREB phosphorylation was reduced in female nicotine place conditioning mice. Our data provide direct evidence that hippocampal Epac signaling is altered in nicotine-induced CPP mice. Pharmacology manipulation Epac signaling may open a new avenue for the treatment of nicotine abuse and dependence.

Highlights

Cigarette smoking is a leading cause of preventable death in the United States and worldwide
We examined the hippocampal Exchange protein directly activated by cAMP (Epac) signaling in nicotine-induced place conditioning mice
Our data provide direct evidence that hippocampal Epac signaling is altered in nicotine-induced conditioned place preference (CPP) mice

Summary

Introduction

Cigarette smoking is a leading cause of preventable death in the United States and worldwide. 15.5% of American adults are current cigarette smokers, with males (17.5%) having a slightly higher rate of use than females (13.5%) [1]. More men than women smoke cigarettes, some studies suggest that female cigarette smokers may be more susceptible to the negative health consequences of tobacco use. Females metabolize nicotine faster, more likely develop respiratory disorders, and have more difficulty with tobacco cessation than male cigarette smokers [2]. Nicotine craving may be more severe in adolescent females than in adolescent males [3]. It is important to identify the differences in behavior and biology related to nicotine exposure between males and females

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