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尼古丁对人类条件反射、消退和复燃的影响。

The effects of nicotine on conditioning, extinction, and reinstatement in humans.

机构信息

Department of Psychological Sciences, University of Connecticut, 406 Babbidge Road, Unit 1020, Storrs, CT, USA.

Department of Psychological Sciences, University of Connecticut, 406 Babbidge Road, Unit 1020, Storrs, CT, USA.

出版信息

Addict Behav. 2018 Feb;77:51-58. doi: 10.1016/j.addbeh.2017.09.008. Epub 2017 Sep 18.

DOI:10.1016/j.addbeh.2017.09.008
PMID:28957728
Abstract

Nicotine has been shown to enhance the reinforcement and reward-responsiveness of non-nicotine stimuli. To determine whether nicotine enhances the strength of conditioning to context, undergraduate participants with varying levels of nicotine dependence were recruited for a two-day study and tested on a virtual reality (VR) conditioned place preference (CPP) paradigm. On day one, participants explored two virtual rooms where they received multiple pairings of M&M rewards in one room and no rewards in the other room, followed by a free-access test session with no rewards. On day two, participants received three test sessions to assess extinction. Subsequently, participants received M&Ms. in a novel context and were then tested for reinstatement. Prior to testing on each day, subjects were administered either nicotine (4mg) or placebo lozenges, in a between-subjects, four-group, 2×2 design (nicotine or placebo on days 1 and 2). After conditioning on day one, only participants who received placebo exhibited a CPP by spending significantly more time in the room previously-paired with M&Ms. Contrary to our hypothesis, nicotine-treated participants did not display a significant CPP, and there were no significant differences between treatment groups. However, post hoc analysis indicated that in a subset of participants with greater nicotine dependence, the nicotine group displayed a CPP by rating the M&M-paired room as significantly more enjoyable than those who received placebo. Additionally, while neither treatment group showed significant place preferences during the first two extinction sessions on Day 2, individuals who received nicotine on Day 1 or placebo on Day 2 spent significantly more time in the M&M-paired room during the final extinction session. Finally, those who received nicotine on Day 2 exhibited significantly greater reinstatement compared to placebo-treated participants. These results partially support preclinical evidence that nicotine can affect learning, extinction, and reinstatement.

摘要

尼古丁已被证明可以增强非尼古丁刺激物的强化和奖励反应性。为了确定尼古丁是否增强了对环境的条件作用强度,我们招募了具有不同尼古丁依赖程度的本科生参加了为期两天的研究,并在虚拟现实(VR)条件性位置偏好(CPP)范式上进行了测试。在第一天,参与者探索了两个虚拟房间,在一个房间中他们获得了多个 M&M 奖励的配对,而在另一个房间中则没有奖励,随后进行了无奖励的自由访问测试。在第二天,参与者进行了三次测试以评估消退。随后,参与者在新环境中接受了 M&M,然后进行了复燃测试。在每天测试之前,受试者以 2×2 设计(第 1 天和第 2 天接受尼古丁或安慰剂),在 4 个组的被试间进行尼古丁(4mg)或安慰剂含片的给药。在第一天进行条件作用后,只有接受安慰剂的参与者在先前与 M&M 配对的房间中花费了明显更多的时间,表现出 CPP。与我们的假设相反,接受尼古丁治疗的参与者并未表现出明显的 CPP,并且治疗组之间没有显着差异。但是,事后分析表明,在一组尼古丁依赖程度较高的参与者中,尼古丁组通过将 M&M 配对的房间评为明显更令人愉快,从而表现出 CPP,而接受安慰剂的参与者则没有。此外,尽管在第 2 天的前两个消退阶段,两个治疗组均未表现出明显的位置偏好,但在第 1 天接受尼古丁或第 2 天接受安慰剂的个体在最后一次消退阶段中在 M&M 配对的房间中花费了明显更多的时间。最后,与接受安慰剂治疗的参与者相比,接受尼古丁治疗的参与者在第 2 天表现出明显更高的复燃率。这些结果部分支持了临床前证据,表明尼古丁可以影响学习,消退和复燃。

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Potent Dopamine D2 Antagonists Block the Reward-Enhancing Effects of Nicotine in Smokers With Schizophrenia.
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