Nicotine serves as an effective reinforcer of intravenous drug-taking behavior in human cigarette smokers
Nicotine serves as an effective reinforcer of intravenous drug-taking behavior in human cigarette smokers
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DOI：
10.1007/s00213-004-1818-6
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发表时间：
2004-09-01
影响因子：
3.4
通讯作者：
Goldberg, SR
中科院分区：
文献类型：
--
作者：
Harvey, DM;Yasar, S;Goldberg, SR
基本原理：尽管许多研究已经证明，尼古丁可以作为动物静脉内自我给药行为的有效抑制剂，但尚未明确显示其在人体中维持高于溶剂安慰剂水平的静脉内自我给药行为。目的：比较尼古丁与生理盐水安慰剂在人类研究志愿者中的强化有效性，这些志愿者在系统性增加反应要求的同时，在静脉给药的固定比例（FR）方案下作出反应。方法：8名男性吸烟者居住在一个住院研究单位。在3小时的会议期间，静脉注射尼古丁和生理盐水可同时进行，并视反应而定（拉动杠杆）。不同受试者在连续治疗期间的尼古丁剂量（0.75、1.5、3.0 mg/注射）、每次注射后的超时（TO）值（1-20 min）和FR反应要求（10-1600）各不相同。结果如下：随着剂量/注射的增加，尼古丁注射次数/疗程显著减少，并且在各种条件下，自我给予尼古丁注射的次数显著大于自我给予生理盐水注射的次数。当FR值随着时间的推移逐渐增加时，尼古丁注射的反应率增加，但盐水注射的反应率没有增加，在最高FR值时反应率最高。在FR值为200及以上时，尼古丁的反应率和注射/疗程率明显且显著高于生理盐水。受试者对尼古丁影响的评价比生理盐水安慰剂明显更积极，也更消极，积极评价明显高于消极评价。结论：尼古丁是一种典型的滥用药物，是吸烟者静脉吸毒行为的有效抑制剂。受试者调整他们的响应响应要求的方式，保持相对恒定的水平，每次尼古丁注射。
Rationale: Although numerous studies have documented that nicotine can function as an effective reinforcer of intravenous self-administration behavior in animals, it has not been clearly shown to maintain intravenous self-administration behavior above vehicle placebo levels in humans. Objectives: To compare the reinforcing effectiveness of nicotine versus saline placebo in human research volunteers responding under fixed-ratio (FR) schedules of intravenous drug self-administration while systematically increasing response requirements. Methods: Eight male cigarette smokers resided in an inpatient research unit. During 3-h sessions, intravenous injections of nicotine and saline were available concurrently and were contingent on responding (pulling a lever). Nicotine dose (0.75, 1.5, 3.0 mg/injection), time out (TO) value after each injection (1-20 min) and FR response requirement (10-1600) were varied in different subjects over consecutive sessions. Results: Number of nicotine injections/session significantly decreased as dose/injection increased and the number of self-administered nicotine injections was significantly greater than the number of self-administered saline injections across conditions. When FR value was progressively increased over sessions, response rates for nicotine, but not saline, injections increased, with maximal rates at the highest FR values. Rates of responding and injections/session were markedly and significantly higher for nicotine than for saline at FR values of 200 and above. Subjects rated effects of nicotine as both significantly more positive and more negative than saline placebo, with positive ratings significantly higher than negative ratings. Conclusions: Nicotine functioned as a prototypic drug of abuse, serving as an effective reinforcer of intravenous drug-taking behavior in human cigarette smokers. Subjects adjusted their responding to response requirements in a way that maintained relatively constant levels of nicotine injections per session.