Cue-induced nicotine-seeking behavior after withdrawal with or without extinction in rats.
Cue-induced nicotine-seeking behavior after withdrawal with or without extinction in rats.
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DOI：
10.1111/adb.12480
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发表时间：
2018-01
影响因子：
3.4
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Markou A;Li J;Tse K;Li X
在戒烟期间暴露在与吸烟相关的环境线索中会引发自我报告的吸烟冲动/渴望，这会导致即使在长期戒烟后也会复发。最近，在人类吸烟者中观察到了线索诱导的戒烟欲望的潜伏期。目前的研究评估了线索诱导的尼古丁寻求行为在不同的戒断条件下，在有尼古丁自我给药史的大鼠中。我们发现，在线索诱导的尼古丁寻求过程中，不同时期的非强化操纵子反应呈现倒U形曲线，戒断后7-21天的反应水平高于戒断1天的反应水平。线索诱导的尼古丁寻求反应是长期的，即使在家中强制戒断42天后也会持续。有趣的是，与受试者之间的评估相比，在同一个人的不同戒断时间点(1、7、14、21和42天)重复测试线索诱导的尼古丁寻求可以减轻反应。此外，尼古丁戒断期间的消退训练显著减少了线索诱导的尼古丁寻求行为的恢复。总之，在尼古丁经历的大鼠中，观察到了对线索诱导的渴望的深刻的时间依赖孵化。此外，重复的线索暴露或消退训练可以减少线索诱导的渴求。在大鼠和人类的研究中，尼古丁渴求现象的潜伏期的证明为通过机制研究发现的大鼠复发治疗靶点的翻译潜力提供了支持。
Exposure to smoking-associated environmental cues during smoke cessation elicits self-reported urge/craving to smoke, which precipitates relapse even after prolonged abstinence. Incubation of cue-induced cigarettes craving during abstinence has been observed in human smokers recently. The present studies assessed cue-induced nicotine-seeking behavior under different withdrawal conditions in rats with a history of nicotine self-administration. We found that non-reinforced operant responding during cue-induced nicotine seeking after different periods of withdrawal from nicotine exhibited an inverted U-shaped curve, with higher levels of responding after 7–21 days of withdrawal than those after 1-day withdrawal. Cue-induced nicotine seeking responding is long-lasting and persists even after 42 days of forced withdrawal in the home cages. Interestingly, repeated testing of cue-induced nicotine seeking at different withdrawal time points (1, 7, 14, 21 and 42 days) in the same individual alleviated responding as compared with the between-subjects assessment. Furthermore, extinction training during nicotine withdrawal significantly decreased cue-induced reinstatement of nicotine-seeking behavior. Together, profound time-dependent incubation of cue-induced craving in nicotine-experienced rats were observed. In addition, repeated cue exposure or extinction training decreases cue-induced craving. The demonstration of incubation of nicotine craving phenomenon in both rat and human studies provides support for the translational potential of therapeutic targets for relapse uncovered through mechanism studies in rats.