Department of Biobehavioral Health, 219 Biobehavioral Health Bldg, The Pennsylvania State University, University Park, PA 16802.
Department of Biobehavioral Health, 219 Biobehavioral Health Bldg, The Pennsylvania State University, University Park, PA 16802.
Pharmacol Biochem Behav. 2018 Feb;165:25-28. doi: 10.1016/j.pbb.2017.12.005. Epub 2017 Dec 16.
Anxiety and stress disorders occur at a higher rate in women compared to men as well as in smokers in comparison to non-smoker population. Nicotine is known to impair fear extinction, which is altered in anxiety disorders. However, nicotine differentially affects fear learning in men and women, which may mean that sex and nicotine-product use can interact to also alter fear extinction. For this study, we examined sex differences in the effects of acute and chronic nicotine administration on fear memory extinction in male and female C57BL/6J mice. To study the acute effects of nicotine, animals trained in a background contextual fear conditioning paradigm were administered nicotine (0.09, 0.18 or 0.36mg/kg) prior to extinction sessions. For chronic nicotine, animals continuously receiving nicotine (12.6, 18, or 24mg/kg/day) were trained in a background contextual fear conditioning paradigm followed by fear extinction sessions. Males exhibited contextual fear extinction deficits following acute and chronic nicotine exposure. Females also exhibited extinction deficits, but only at the highest doses of acute nicotine (0.36mg/kg) while chronic nicotine did not result in extinction deficits in female mice. These results suggest that sex mediates sensitivity to nicotine's effects on contextual fear memory extinction.
焦虑和压力障碍在女性中的发生率高于男性，在吸烟者中的发生率也高于非吸烟者。已知尼古丁会损害恐惧的消除，而恐惧的消除在焦虑障碍中会发生改变。然而，尼古丁会对男性和女性的恐惧学习产生不同的影响，这可能意味着性别和尼古丁产品的使用会相互作用，从而改变恐惧的消除。在这项研究中，我们研究了急性和慢性尼古丁给药对雄性和雌性 C57BL/6J 小鼠恐惧记忆消除的影响中的性别差异。为了研究尼古丁的急性作用，在背景条件性恐惧训练范式中接受训练的动物在消除阶段之前给予尼古丁（0.09、0.18 或 0.36mg/kg）。对于慢性尼古丁，连续接受尼古丁（12.6、18 或 24mg/kg/天）的动物在背景条件性恐惧训练范式中接受训练，然后进行恐惧消除阶段。雄性在急性和慢性尼古丁暴露后表现出背景恐惧消除缺陷。雌性也表现出消除缺陷，但仅在急性尼古丁的最高剂量（0.36mg/kg）下，而慢性尼古丁在雌性小鼠中不会导致消除缺陷。这些结果表明，性别调节了对尼古丁影响背景恐惧记忆消除的敏感性。
