Caldarone Barbara J, King Sarah L, Picciotto Marina R
Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT 06508, USA.
Neurosci Lett. 2008 Jul 11;439(2):187-91. doi: 10.1016/j.neulet.2008.05.023. Epub 2008 May 13.
Smoking appears to increase overall levels of stress, despite self-reports that men and women smoke to control symptoms of anxiety. The overall incidence of anxiety disorders is also significantly higher in women. This study examined whether behavioral sensitivity to chronic nicotine varies across sexes in mice. Male and female C57BL/6J mice were exposed chronically to nicotine in the drinking water (50, 100, or 200 microg/ml) and tested for locomotor activation and anxiety-like behavior in the elevated plus maze (EPM). Female mice were less sensitive to the locomotor activating effects of chronic nicotine. Whereas both males and females showed increases in locomotor activity at the highest (200 microg/ml) concentration of nicotine, only males showed locomotor activation at the middle (100 microg/ml) concentration. The decreased sensitivity in females could not be explained by reduced nicotine intake compared to males. In the EPM, nicotine produced an anxiogenic-like response in females, but had no effect in males. Treatment with the high (200 microg/ml) dose of nicotine reduced the amount of time spent in the open arms of the EPM in female, but not male mice. No differences in the anxiogenic-like response to chronic nicotine was observed between beta2-subunit knockout and wildtype mice, suggesting that beta2-subunit containing nicotinic receptors do not mediate the anxiogenic-like response to chronic nicotine in females. This shows that female mice have an anxiogenic-like response to chronic nicotine, but are less sensitive to nicotine's psychostimulant properties, which may be related to the increased relapse to smoking following abstinence in women.
尽管有自我报告称男性和女性吸烟是为了控制焦虑症状，但吸烟似乎会增加总体压力水平。女性焦虑症的总体发病率也显著更高。本研究考察了小鼠对慢性尼古丁的行为敏感性是否存在性别差异。将雄性和雌性C57BL/6J小鼠长期暴露于饮用水中的尼古丁（50、100或200微克/毫升），并在高架十字迷宫（EPM）中测试其运动激活和焦虑样行为。雌性小鼠对慢性尼古丁的运动激活作用不太敏感。虽然雄性和雌性在最高（200微克/毫升）尼古丁浓度下均表现出运动活动增加，但只有雄性在中等（100微克/毫升）浓度下表现出运动激活。与雄性相比，雌性敏感性降低不能用尼古丁摄入量减少来解释。在EPM中，尼古丁在雌性小鼠中产生了类似焦虑的反应，但对雄性小鼠没有影响。高剂量（200微克/毫升）尼古丁处理减少了雌性小鼠在EPM开放臂中停留的时间，但对雄性小鼠没有影响。在β2亚基敲除小鼠和野生型小鼠之间未观察到对慢性尼古丁的类似焦虑反应的差异，这表明含有β2亚基的烟碱受体不介导雌性小鼠对慢性尼古丁的类似焦虑反应。这表明雌性小鼠对慢性尼古丁有类似焦虑的反应，但对尼古丁的精神兴奋特性不太敏感，这可能与女性戒烟后吸烟复吸率增加有关。
