Effects of menthol and its interaction with nicotine-conditioned cue on nicotine-seeking behavior in rats.
Effects of menthol and its interaction with nicotine-conditioned cue on nicotine-seeking behavior in rats.
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DOI：
10.1007/s00213-017-4736-0
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发表时间：
2017-12
影响因子：
3.4
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Harrison E;Biswas L;Avusula R;Zhang M;Gong Y;Liu X
越来越多的临床证据表明，薄荷醇，烟草产品中的重要调味添加剂，可能有助于吸烟和尼古丁依赖。吸烟行为的复发对烟草成瘾的治疗提出了严峻的挑战。一个尚未解决的问题是，烟草制品的薄荷化是否会促使戒烟者复吸烟草。本研究探讨了薄荷醇对大鼠尼古丁寻求行为的持久性和复发的影响。训练雄性Sprague-Dawley大鼠按下杠杆，在固定比例强化方案下进行静脉内尼古丁自我给药（0.03 mg/kg/输注）。每次尼古丁输注都通过呈现感官刺激来发出信号，该感官刺激被建立为离散的尼古丁条件性线索。在治疗前5分钟，大鼠接受腹膜内注射薄荷醇（0.1 mg/kg）或溶媒。在随后的消退测试中，尼古丁在有或没有薄荷醇和/或尼古丁条件提示的情况下不可用。在满足消退标准后的第二天进行恢复试验。此外，还测试了食物寻求反应。在尼古丁训练的大鼠亚组中，在薄荷醇给药前给予TRPM 8拮抗剂RQ-00203078。在消退试验中，持续给予薄荷醇对先前活性和尼古丁增强的杠杆产生持续反应。消退后重新给予薄荷醇恢复了主动杠杆反应。在消退和恢复测试中，在会话期间，会话前薄荷醇管理和提示重新呈现的组合比薄荷醇或单独的提示产生了更强大的行为效果。在食物训练的大鼠中没有观察到薄荷醇的这种作用。RQ-00203078未改变薄荷醇对尼古丁寻求的影响。这些数据表明，薄荷醇特异性地维持和恢复尼古丁寻求行为，并且这种作用不依赖于TRPM 8活性。这些研究结果表明，大多数烟草产品中的薄荷醇，即使没有薄荷醇标记，也可能有助于烟草寻求行为的持续和复发。
Increasing clinical evidence suggests that menthol, a significant flavoring additive in tobacco products, may contribute to smoking and nicotine dependence. Relapse to smoking behavior presents a formidable challenge for the treatment of tobacco addiction. An unresolved issue is whether the mentholation of tobacco products precipitates relapse to tobacco use in abstinent smokers. The present study examined the effects of menthol on the perseverance and relapse of nicotine-seeking behavior in rats. Male Sprague-Dawley rats were trained to press a lever for intravenous nicotine self-administration (0.03 mg/kg/infusion) under a fixed-ratio 5 schedule of reinforcement. Each nicotine infusion was signaled by the presentation of a sensory stimulus that was established as a discrete nicotine-conditioned cue. Five minutes prior to the sessions, the rats received an intraperitoneal injection of menthol (0.1 mg/kg) or vehicle. In the subsequent extinction test sessions, nicotine was unavailable with or without menthol and/or the nicotine-conditioned cue. The reinstatement tests were performed the following day after the extinction criterion was met. Menthol was also tested on food-seeking responses. In a subset of nicotine-trained rats, a TRPM8 antagonist RQ-00203078 was given prior to menthol administration. Continued administration of menthol sustained responses on the previously active and nicotine-reinforced lever in the extinction tests. The re-administration of menthol after extinction reinstated active lever responses. In both the extinction and reinstatement tests, a combination of pre-session menthol administration and cue re-presentation during the session produced a more robust behavioral effect than either menthol or the cue alone. No such effects of menthol was observed in food trained rats. RQ-00203078 did not change menthol effect on nicotine seeking. These data demonstrated that menthol specifically sustained and reinstated nicotine-seeking behavior and this effect was independent of TRPM8 activity. These findings suggest that menthol in most tobacco products, even not menthol-labeled, may contribute to the perseverance of and relapse to tobacco-seeking behavior.
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影响因子：
5.2
作者：
Anderson, Stacey J.
通讯作者：
Anderson, Stacey J.
影响因子：
3.7
作者：
Ashoor, Abrar;Nordman, Jacob C.;Oz, Murat
通讯作者：
Oz, Murat
影响因子：
3.4
作者：
Cervo, Luigi;Di Clemente, Angelo;Bifone, Angelo
通讯作者：
Bifone, Angelo
影响因子：
3.4
作者：
Barker DJ;Bercovicz D;Servilio LC;Simmons SJ;Ma S;Root DH;Pawlak AP;West MO
通讯作者：
West MO
DOI：
10.1073/pnas.98.4.1976
发表时间：
2001-02-13
影响因子：
11.1
作者：
Ciccocioppo, R;Sanna, PP;Weiss, F
通讯作者：
Weiss, F