Philosophical Transactions of the Royal Society B: Biological Sciences
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Context-induced relapse to drug seeking: a review

Hans S Crombag

Hans S Crombag

Behavioural and Clinical Neuroscience Group, Department of Psychology, School of Life Sciences, The University of SussexBrighton BN1 9RH, UK

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Jennifer M Bossert

Jennifer M Bossert

Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, NIH/DHHS251 Bayview Blvd, Baltimore, MD 21224, USA

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Eisuke Koya

Eisuke Koya

Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, NIH/DHHS251 Bayview Blvd, Baltimore, MD 21224, USA

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Yavin Shaham

Yavin Shaham

Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, NIH/DHHS251 Bayview Blvd, Baltimore, MD 21224, USA

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    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.

    Footnotes

    †These authors contributed equally to this review.

    References