尼古丁对乙醇强化作用的奖赏增强效应的性别差异：强化物需求分析。
Sex Differences in the Reward-Enhancing Effects of Nicotine on Ethanol Reinforcement: A Reinforcer Demand Analysis.
机构信息
Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE.
Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE.
出版信息
Nicotine Tob Res. 2020 Feb 6;22(2):238-247. doi: 10.1093/ntr/ntz056.
BACKGROUND
Alcohol is often consumed with tobacco, and dependence to alcohol and tobacco are highly comorbid. In addition, there are differences in the prevalence of nicotine- and alcohol-abuse between the sexes. Nicotine produces enhancing effects on the value of other reinforcers, which may extend to alcohol.
METHODS
Male and female Wistar rats were trained to self-administer 15% ethanol solution in 30-minute sessions. Once ethanol self-administration was established, demand for ethanol was evaluated using an exponential reinforcer demand method, in which the response cost per reinforcer delivery was systematically increased over blocks of several sessions. Within each cost condition, rats were preinjected with nicotine (0.05, 0.1, 0.2, or 0.4 mg/kg base, SC) or saline 5 minutes before self-administration sessions. The effects of nicotine dose and biological sex were evaluated using the estimates generated by the reinforcer demand model.
RESULTS
Under saline conditions, males showed greater sensitivity to ethanol reinforcement than females. Nicotine enhanced the reinforcement value of alcohol and this varied with sex. In both sexes, 0.4 mg/kg nicotine decreased intensity of ethanol demand. However, 0.05, 0.1, and 0.2 mg/kg nicotine decreased elasticity of ethanol demand in females, but not in males.
CONCLUSIONS
Nicotine enhances ethanol reinforcement, which may partially drive comorbidity between nicotine-abuse and alcohol-abuse. Males showed signs of greater ethanol reinforcement value than females under saline conditions, and nicotine attenuated this effect by increasing ethanol reinforcement value in the females. These findings highlight that a complete understanding of alcohol-abuse must include a thorough study of alcohol use in the context of other drug use, including nicotine.
IMPLICATIONS
Nicotine dose dependently enhances the alcohol reinforcement value in a manner that is clearly influenced by biological sex. Under saline baseline conditions, males show lower elasticity of demand for alcohol reinforcement than females, indicative of greater reinforcement value. However, nicotine attenuated this difference by enhancing alcohol reward in the females. Specifically, low-to-moderate doses (0.05-0.2 mg/kg) of nicotine decreased elasticity of alcohol demand in female rats, increasing the perseverance of their alcohol taking behavior. These data indicate that the well-documented reward-enhancing effects of nicotine on sensory reinforcement extend to alcohol reinforcement and that these vary with biological sex.
背景
酒精经常与烟草一起被消费，而且酒精和烟草依赖高度共病。此外，尼古丁和酒精滥用的发生率在性别之间存在差异。尼古丁对其他强化物的价值产生增强作用，这可能扩展到酒精。
方法
雄性和雌性 Wistar 大鼠在 30 分钟的时间段内接受 15%乙醇溶液的自我给药。一旦建立了乙醇自我给药，就使用指数强化物需求方法评估对乙醇的需求，其中每个强化物的响应成本在几个会话的块中被系统地增加。在每个成本条件下，大鼠在自我给药前 5 分钟接受尼古丁（0.05、0.1、0.2 或 0.4mg/kg 基础，SC）或生理盐水预处理。使用强化物需求模型生成的估计值评估尼古丁剂量和生物性别对其的影响。
结果
在生理盐水条件下，雄性对酒精强化的敏感性大于雌性。尼古丁增强了酒精的强化价值，并且这种作用因性别而异。在两种性别中，0.4mg/kg 尼古丁降低了乙醇需求的强度。然而，0.05、0.1 和 0.2mg/kg 尼古丁降低了雌性而非雄性乙醇需求的弹性。
结论
尼古丁增强了乙醇的强化作用，这可能部分导致尼古丁滥用和酒精滥用之间的共病。在生理盐水条件下，雄性显示出比雌性更高的乙醇强化价值的迹象，而尼古丁通过增加雌性的乙醇强化价值来减弱这种作用。这些发现强调，对酒精滥用的全面理解必须包括在其他药物使用（包括尼古丁）背景下对酒精使用的彻底研究。
意义
尼古丁以明显受生物性别影响的方式依赖性地增强酒精的强化价值。在生理盐水基线条件下，雄性对酒精强化的需求弹性低于雌性，表明强化价值更高。然而，尼古丁通过增强雌性的酒精奖赏来减弱这种差异。具体而言，低至中等剂量（0.05-0.2mg/kg）的尼古丁降低了雌性大鼠对酒精需求的弹性，增加了她们饮酒行为的坚持力。这些数据表明，尼古丁对感官强化的有记录的增强作用扩展到酒精强化，并且这些作用因生物性别而异。
Zotero 插件