Extinction of Conditioned Responses to Methamphetamine-Associated Stimuli in Healthy Humans.
Extinction of Conditioned Responses to Methamphetamine-Associated Stimuli in Healthy Humans.
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DOI：
10.1007/s00213-016-4297-7
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发表时间：
2016-07
影响因子：
3.4
通讯作者：
de Wit H
中科院分区：
文献类型：
--
作者：
Cavallo JS;Ruiz NA;de Wit H
在药物体验过程中出现的情境刺激通过巴甫洛夫条件反射与药物相关，并被认为是维持药物寻求行为的原因。因此，条件反应的消退是治疗的重要目标。迄今为止，药物配对线索的获得和消退已经在动物模型或药物依赖个体中进行了研究，但很少在非吸毒者中进行。我们最近开发了一个程序来研究健康志愿者单剂量甲基苯丙胺（MA）后条件反应的获得。在这里，我们研究了这些反应的消退和它们在条件反射后的持续性。健康成人（18-35岁; N=20）接受两对视听刺激与MA（20 mg口服）或安慰剂。对刺激的反应进行了评估之前和之后的条件反射，使用三个任务：行为偏好，注意力偏差，和主观的“喜欢”。受试者表现出的药物配对刺激的行为偏好在第一个后处理测试，但这在随后的灭绝测试迅速下降。他们还表现出一种偏见，最初看向药物配对刺激在第一次后测试会议，但不是此后。受试者在条件反射过程中经历了更多积极的主观药物作用，在消退阶段表现出较小的偏好下降。此外，在消退阶段较长的会话间间隔与行为偏好测量的消退程度较低相关。条件反应后，两个配对与MA迅速熄灭，并受主观药物效应和熄灭间隔。表征和完善这一条件反射过程将有助于理解人类药物相关条件反射的获得和消退过程。
Contextual stimuli present during drug experiences become associated with the drug through Pavlovian conditioning, and are thought to sustain drug-seeking behavior. Thus, extinction of conditioned responses is an important target for treatment. To date, acquisition and extinction to drug-paired cues have been studied in animal models or drug-dependent individuals, but rarely in non drug-users. We have recently developed a procedure to study acquisition of conditioned responses after single doses of methamphetamine (MA) in healthy volunteers. Here we examined extinction of these responses and their persistence after conditioning. Healthy adults (18–35 yrs; N=20) received two pairings of audio-visual stimuli with MA (20 mg oral) or placebo. Responses to stimuli were assessed before and after conditioning, using three tasks: behavioral preference, attentional bias, and subjective ‘liking.’ Subjects exhibited behavioral preference for the drug-paired stimuli at the first post-conditioning test, but this declined rapidly on subsequent extinction tests. They also exhibited a bias to initially look towards the drug-paired stimuli at the first post-test session, but not thereafter. Subjects who experienced more positive subjective drug effects during conditioning exhibited a smaller decline in preference during the extinction phase. Further, longer inter-session intervals during the extinction phase were associated with less extinction of the behavioral preference measure. Conditioned responses after two pairings with MA extinguish quickly, and are influenced by both subjective drug effects and the extinction interval. Characterizing and refining this conditioning procedure will aid in understanding the acquisition and extinction processes of drug-related conditioned responses in humans.