Program in Behavioral Neuroscience, University of South Carolina, Columbia, SC 29208, USA.
Program in Behavioral Neuroscience, University of South Carolina, Columbia, SC 29208, USA.
Pharmacol Biochem Behav. 2018 Feb;165:14-24. doi: 10.1016/j.pbb.2017.12.003. Epub 2017 Dec 19.
In those who use nicotine, the likelihood of dependence, negative health consequences, and failed treatment outcomes differ as a function of gender. Women may be more sensitive to learning processes driven by repeated nicotine exposure that influence conditioned approach and craving. Sex differences in nicotine's influence over overt behaviors (i.e. hypoactivity or behavioral sensitization) can be examined using passive drug administration models in male and female rats. Following repeated intravenous (IV) nicotine injections, behavioral sensitization is enhanced in female rats compared to males. Nonetheless, characteristics of the testing environment also mediate rodent behavior following drug administration. The current experiment used a within-subjects design to determine if nicotine-induced changes in horizontal activity, center entries, and rearing displayed by male and female rats is detected when behavior was recorded in round vs. square chambers. Behaviors were recorded from each group (males-round: n=19; males-square: n=18; females-square: n=19; and females-round: n=19) immediately following IV injection of saline, acute nicotine, and repeated nicotine (0.05mg/kg/injection). Prior to nicotine treatment, sex differences were apparent only in round chambers. Following nicotine administration, the order of magnitude for the chamber that provided enhanced detection of hypoactivity or sensitization was contingent upon both the dependent measure under examination and the animal's biological sex. As such, round and square testing chambers provide different, and sometimes contradictory, accounts of how male and female rats respond to nicotine treatment. It is possible that a central mechanism such as stress or cue sensitivity is impacted by both drug exposure and environment to drive the sex differences observed in the current experiment. Until these complex relations are better understood, experiments considering sex differences in drug responses should balance characteristics of the testing environment to provide a complete interpretation of drug-induced changes to behavior.
在使用尼古丁的人群中，依赖的可能性、负面健康后果和治疗结果的失败因性别而异。女性可能对受重复尼古丁暴露驱动的学习过程更敏感，这些过程影响条件性接近和渴望。可以使用雄性和雌性大鼠的被动药物给药模型来检查尼古丁对明显行为（即活动减少或行为敏感化）的影响中的性别差异。在雄性和雌性大鼠中，重复静脉内（IV）尼古丁注射后，雌性大鼠的行为敏感化增强。尽管如此，药物给药后，测试环境的特征也会调节啮齿动物的行为。当前实验使用了一个被试内设计，以确定当在圆形和方形室中记录行为时，雄性和雌性大鼠的水平活动、中心进入和竖起次数是否会因尼古丁引起的变化而改变。每组（雄性圆形：n=19；雄性方形：n=18；雌性方形：n=19；雌性圆形：n=19）在 IV 注射盐水、急性尼古丁和重复尼古丁（0.05mg/kg/注射）后立即记录行为。在尼古丁治疗之前，只有在圆形室中才会出现性别差异。在尼古丁给药后，检测活动减少或敏感化的增强的室的数量级取决于所检查的因变量和动物的生物性别。因此，圆形和方形测试室提供了不同的，有时甚至是矛盾的，说明雄性和雌性大鼠对尼古丁治疗的反应。可能是一种中枢机制，如应激或线索敏感性，受到药物暴露和环境的共同影响，从而导致了当前实验中观察到的性别差异。在这些复杂的关系得到更好的理解之前，考虑药物反应性别差异的实验应该平衡测试环境的特征，以提供对行为的药物诱导变化的完整解释。
