Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences
Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences
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DOI：
10.1038/npp.2015.373
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发表时间：
2016-07-01
影响因子：
7.6
通讯作者：
Sofuoglu, Mehmet
中科院分区：
文献类型：
--
作者：
Jensen, Kevin P.;DeVito, Elise E.;Sofuoglu, Mehmet
尼古丁敏感性的性别差异可能会影响烟草依赖的脆弱性。本研究的目的是研究男性和女性吸烟者静脉注射尼古丁的强化和主观效应的剂量反应函数。烟草依赖受试者（12名男性和14名女性）参加了四个实验阶段，其中他们在随机双盲交叉设计中接受了盐水和尼古丁（0.1，0.2，0.3或0.4 mg剂量）的样品输注。在每个疗程中，受试者首先接受样品输注，并监测心率（HR）、血压和主观刺激、愉快和厌恶反应。在6项双盲强制选择试验中，样本输注后，受试者立即自我给予尼古丁或生理盐水。在尼古丁选择范例中观察到性别与剂量的相互作用。男性的尼古丁自我给药率与尼古丁剂量呈负相关（男性对低剂量尼古丁的选择偏好高于高剂量尼古丁），但女性的剂量与选择偏好之间无显著相关性。与安慰剂相比，样本剂量的尼古丁增加了心率和血压，并诱导了刺激性、愉悦性和厌恶性主观效应。雄性动物的舒张压呈剂量依赖性增加，但雌性动物中无此现象。这些结果表明，在接近强化阈值的剂量下，尼古丁自我给药存在性别差异，表明男性和女性吸烟者可能对可用于自我给药的尼古丁剂量变化有不同的反应。
Sex differences in the sensitivity to nicotine may influence vulnerability to tobacco dependence. The goal of this study was to investigate the dose response function for the reinforcing and subjective effects of intravenous nicotine in male and female smokers. Tobacco-dependent subjects (12 male and 14 female) participated in four experimental sessions in which they received sample infusions of saline and nicotine (0.1, 0.2, 0.3, or 0.4 mg doses) in a randomized double-blind crossover design. During each session, subjects first received the sample infusions, and heart rate (HR), blood pressure, and subjective stimulatory, pleasurable and aversive responses were monitored. Immediately following the sample infusions, subjects self-administered either nicotine or saline in six double-blind forced-choice trials. A sex by dose interaction was observed in the nicotine choice paradigm. Nicotine self-administration rate was negatively correlated with nicotine dose in males (males displayed choice preference for low doses of nicotine over high doses of nicotine), but no significant relationship between dose and choice preference was evident in females. Relative to placebo, sample doses of nicotine increased heart rate and blood pressure, and induced stimulatory, pleasurable, and aversive subjective effects. Diastolic blood pressure increased dose dependently in males, but not in females. These findings, which demonstrate sex differences in nicotine self-administration for doses that are near to the reinforcement threshold, suggest that male and female smokers may respond differently to the changes in nicotine doses available for self-administration.