The Winding Road to Relapse: Forging a New Understanding of Cue-Induced Reinstatement Models and Their Associated Neural Mechanisms.

Mark D Namba,M Foster Olive,Joshua S Beckmann,Cassandra D Gipson,Seven E Tomek

doi:10.3389/fnbeh.2018.00017

Mark D Namba, M Foster Olive + Show 3 more

Open Access

https://doi.org/10.3389/fnbeh.2018.00017

Copy DOI

Abstract

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.

Highlights

Relapse triggered by cues associated with drugs of abuse is a hallmark of addiction and is a primary contributor to impeding success in maintaining abstinence
We propose that the models discussed are useful in determining the differential neurobiological substrates underlying various types of motivated behavior and that care should be taken to better dissociate the roles of different types of cues in models of relapse
As we have attempted to highlight in this review, there is a tendency in the substance use disorder literature to posit the stimulus control of drug-associated behavior as the product of a single, unitary Pavlovian process

Summary

INTRODUCTION

Relapse triggered by cues associated with drugs of abuse is a hallmark of addiction and is a primary contributor to impeding success in maintaining abstinence. Discrete SDs have been used to study stimulus control of drug seeking, where specific stimuli can be used to signal the availability of drug, the non-availability of drug, or the availability of a non-drug reinforcer (e.g., food; Weissenborn et al, 1995; Weiss et al, 2000, 2001, 2003; Stairs et al, 2010; McCuddy et al, 2014), all upon a specific operant response This approach relies on the use of a multiple schedule, where changes in response-outcome contingency are split into components that are differentially signaled by a specific stimulus change throughout training. Following extinction of responses to either lever in the absence of either SD, non-contingent re-exposure to the previously trained SDs alone will increase the response associated with that SD As discussed above, both CSs used as conditioned reinforcers and non-contingent exposure to SDs can reinstate drug-seeking behavior, it appears they do so through different neurobehavioral processes.

Findings

DISCUSSION

CONCLUSIONS