We assessed if there were any sex-related differences in the ability of nicotine to increase plasma corticosterone secretion after single or repeated nicotine administration. For single-dose studies, male and female mice were habituated to the test room for 1 h and injected with saline or nicotine (0.25 or 1 mg/kg, subcutaneously (s.c.)). In repeated-dosing studies, mice were injected with saline or nicotine (1 mg/kg, s.c.) once daily for six days, and, on day 7, received nicotine (1 mg/kg, s.c.). Mice were then euthanized 15 min later, and trunk blood was collected for the measurement of corticosterone, nicotine, and cotinine. Our results showed that saline or nicotine each significantly increased plasma corticosterone levels in both males and females, with a greater response in female mice. Plasma corticosterone levels were increased in male but not female mice after being treated repeatedly compared to single nicotine administration. The level of cotinine, a biomarker of nicotine use, was significantly higher in female than in male mice. Taken together, these novel findings suggest that female mice respond to nicotine and the stress of handling more than male mice and provide for the first-time quantitative data on male–female differences in nicotine-induced elevations of corticosterone and cotinine plasma levels.

中文翻译：

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性别对尼古丁诱导的C57BL / 6J小鼠血浆皮质酮和可替宁水平变化的影响

我们评估了单次或重复给予尼古丁后，尼古丁增加血浆皮质类固醇分泌的能力是否存在任何性别相关的差异。对于单剂量研究，将雄性和雌性小鼠习惯化至测试室1小时，并注射盐水或尼古丁（0.25或1 mg / kg，皮下注射（sc））。在重复给药研究中，每天一次给小鼠注射生理盐水或尼古丁（1 mg / kg，皮下注射），持续六天，并在第7天接受尼古丁（1 mg / kg，皮下注射）。然后在15分钟后对小鼠实施安乐死，并收集躯干血液以测量皮质酮，尼古丁和可替宁。我们的研究结果表明，生理盐水或尼古丁均显着增加了雄性和雌性血浆皮质酮水平，雌性小鼠的反应也更大。与单次尼古丁给药相比，经过反复治疗的雄性小鼠血浆皮质类固醇水平升高，但雌性小鼠没有升高。雌性烟碱的生物标志物可替宁的水平在雌性小鼠中明显高于雄性小鼠。综上所述，这些新颖的发现表明，雌性小鼠对尼古丁的反应和承受压力要比雄性小鼠更多，并首次提供了有关尼古丁引起的皮质酮和可替宁血浆水平升高的男女差异的定量数据。