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.

中文翻译：

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行为和海马Epac信号转导小鼠尼古丁CPP。

吸烟是美国乃至全世界公共卫生的主要挑战。许多研究表明，成年男性和女性对吸烟的反应不同，但是关于吸烟对男性和女性影响的神经生物学研究有限。被cAMP（Epac）信号直接激活的交换蛋白参与了成瘾行为。在这项研究中，我们检查了尼古丁诱发的位置调节小鼠的海马Epac信号传导。0.2 mg / kg和0.4 mg / kg的尼古丁分别在雄性和雌性小鼠中诱发条件性位置偏爱（CPP）。CPP后，雄性小鼠表现出较少的焦虑样行为，如开放式试验所证实。在雄性和雌性尼古丁场所调节小鼠中海马Epac2蛋白均升高。然而，在雌性尼古丁场所调节小鼠中，Rap1蛋白升高，CREB磷酸化降低。我们的数据提供了直接证据，表明尼古丁诱导的CPP小鼠海马Epac信号发生改变。药理学操作Epac信号传导可能为治疗尼古丁滥用和依赖性开辟新途径。