In drug addiction, cues previously associated with drug use can produce craving and frequently trigger the resumption of drug taking in individuals vulnerable to relapse. Environmental stimuli associated with drugs or natural reinforcers can become reliably conditioned to increase behavior that was previously reinforced. In preclinical models of addiction, these cues enhance both drug self-administration and reinstatement of drug seeking. In this review, we will dissociate the roles of conditioned stimuli as reinforcers from their modulatory or discriminative functions in producing drug-seeking behavior. As well, we will examine possible differences in neurobiological encoding underlying these functional differences. Specifically, we will discuss how models of drug addiction and relapse should more systematically evaluate these different types of stimuli to better understand the neurobiology underlying craving and relapse. In this way, behavioral and pharmacotherapeutic interventions may be better tailored to promote drug use cessation outcomes and long-term abstinence.

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Published in Frontiers in Behavioral Neuroscience, v. 12, article 17, p. 1-22.

Copyright © 2018 Namba, Tomek, Olive, Beckmann and Gipson.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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This work was supported by Public Health Service grants R00 DA036569 and DA036569–S1 (CG), AA AA025590 and DA043172 (MFO), and R00 DA033373 (JB) from the National Institutes of Health.