Crombag Hans S, Bossert Jennifer M, Koya Eisuke, Shaham Yavin
Department of Psychology, Behavioural and Clinical Neuroscience Group, School of Life Sciences, The University of Sussex, Brighton, UK.
Philos Trans R Soc Lond B Biol Sci. 2008 Oct 12;363(1507):3233-43. doi: 10.1098/rstb.2008.0090.
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.
在人类中，暴露于先前与药物摄入相关的环境中常常会引发药物使用的复发，但介导这种复发的机制尚不清楚。基于布顿（Bouton）和博尔斯（Bolles）早期关于情境诱导的习得行为“恢复”的研究，我们开发了一种程序来研究情境诱导的觅药行为复发。在这个程序中，首先训练大鼠在一种情境中自我给药。接下来，在不同的（非药物）情境中消除药物强化的杠杆反应。随后，通过将大鼠重新暴露于与药物相关的情境中来评估情境诱导的觅药行为恢复。使用该程序的变体，我们和其他人报告了在有海洛因、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中可靠的情境诱导恢复。在这里，我们首先讨论情境诱导恢复的潜在心理机制，包括兴奋性和抑制性巴甫洛夫条件反射以及情境设定。然后，我们总结了药理学和神经解剖学研究的结果，这些研究涉及几种神经递质系统（多巴胺、谷氨酸、血清素和阿片类物质）和脑区（腹侧被盖区、伏隔核壳、背侧纹状体、基底外侧杏仁核、前额叶皮层、背侧海马体和外侧下丘脑）在情境诱导恢复中的作用。我们通过讨论大鼠研究对情境诱导的觅药行为恢复的临床意义来得出结论。
