Context-induced relapse to drug seeking: a review
Context-induced relapse to drug seeking: a review
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DOI：
10.1098/rstb.2008.0090
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发表时间：
2008-10-12
影响因子：
6.3
通讯作者：
Shaham, Yavin
中科院分区：
文献类型：
--
作者：
Crombag, Hans S.;Bossert, Jennifer M.;Shaham, Yavin
在人类中，暴露于先前与药物摄入相关的环境背景通常会引起药物使用的复发，但介导这种复发的机制尚不清楚。基于Bouton和Bolles对环境诱导的习得行为“更新”的早期研究，我们开发了一种研究环境诱导的药物寻求复发的程序。在该程序中，首先训练大鼠在一种情况下自我给药。接下来，药物增强的杠杆反应在不同的（非药物）环境中消失。随后，通过将大鼠重新暴露于药物相关背景来评估背景诱导的药物寻求恢复。使用该程序的变体，我们和其他人报告了具有海洛因、可卡因、海洛因-可卡因组合、酒精和尼古丁自我给药史的大鼠的可靠的上下文诱导的恢复。在这里，我们首先讨论了潜在的心理机制，上下文诱导的恢复，包括兴奋性和抑制性巴甫洛夫条件反射，和场合设置。然后，我们总结了一些神经递质系统（多巴胺，谷氨酸，5-羟色胺和阿片类药物）和脑区（腹侧被盖区，海马壳，背侧纹状体，基底外侧杏仁核，前额叶皮层，背侧海马和外侧下丘脑）的作用的药理学和神经解剖学研究的结果在上下文诱导的恢复。最后，我们讨论了背景诱导的药物寻求恢复大鼠研究的临床意义。
In humans, exposure to environmental contexts previously associated with drug intake often provokes relapse to drug use, but the mechanisms mediating this relapse are unknown. Based on early studies by Bouton & Bolles on context-induced 'renewal' of learned behaviours, we developed a procedure to study context-induced relapse to drug seeking. In this procedure, rats are first trained to self-administer drug in one context. Next, drug-reinforced lever responding is extinguished in a different (non-drug) context. Subsequently, context-induced reinstatement of drug seeking is assessed by re-exposing rats to the drug-associated context. Using variations of this procedure, we and others reported reliable context-induced reinstatement in rats with a history of heroin, cocaine, heroin-cocaine combination, alcohol and nicotine self-administration. Here, we first discuss potential psychological mechanisms of context-induced reinstatement, including excitatory and inhibitory Pavlovian conditioning, and occasion setting. We then summarize results from pharmacological and neuroanatomical studies on the role of several neurotransmitter systems (dopamine, glutamate, serotonin and opioids) and brain areas (ventral tegmental area, accumbens shell, dorsal striatum, basolateral amygdala, prefrontal cortex, dorsal hippocampus and lateral hypothalamus) in context-induced reinstatement. We conclude by discussing the clinical implications of rat studies on context-induced reinstatement of drug seeking.