Considering Drug-Associated Contexts in Substance Use Disorders and Treatment Development

Abstract

Environmental contexts that are reliably associated with the use of pharmacologically active substances are hypothesized to contribute to substance use disorders. In this review, we provide an updated summary of parallel preclinical and human studies that support this hypothesis. Research conducted in rats shows that environmental contexts that are reliably paired with drug use can renew extinguished drug-seeking behavior and amplify responding elicited by discrete, drug-predictive cues. Akin to drugassociated contexts, interoceptive drug stimuli produced by the psychopharmacological effects of drugs can also influence learning and memory processes that play a role in substance use disorders. Findings from human laboratory studies show that drug-associated contexts, including social stimuli, can have profound effects on cue reactivity, drug use, and drug-related cognitive expectancies. This translationally relevant research supports the idea that treatments for substance use disorders could be improved by considering drug-associated contexts as a factor in treatment interventions. We conclude this review with ideas for how to integrate drug-associated contexts into treatment-oriented research based on 4 approaches: pharmacology, brain stimulation, mindfulness-based relapse prevention, and cognitive behavioral group therapy. Throughout, we focus on alcoholand tobacco-related research, which are two of the most prevalent and commonly misused drugs worldwide for which there are known treatments.

Drug-Induced Conditioned Place Preference and Its Practical Use in Substance Use Disorder Research

“…The ability to reinstate CPP is indicative of persistent drug-associated memories, which likely results in the propensity to elicit drug cravings and/or directs drug-seeking long into abstinence (O’Brien et al, 1986 , 1992 ). Furthermore, work by LeCocq et al ( 2020 ) has advocated the ability of drug-associated contexts to serve as a vital trigger for reinstatement and renewal of extinguished addiction-like behaviors.…”

“…Through repetitive pairings with drug use, contexts that were previously neutral gain incentive salience, and this intense association can serve to reinforce the cyclical nature of drug-seeking behaviors. In animal models of drug abuse, the ABA renewal paradigm [whereby the subject is conditioned in one context (A), extinguished in another (B), and is then re-exposed to the original context (A)] emphasizes how environmental contexts that have been associated with drug use can directly prompt reinstatement (LeCocq et al, 2020 ). Clinical research has established that drug-associated contexts promote cue reactivity, elevate craving responses, and are sufficient to elicit context-induced relapse (LeCocq et al, 2020 ).…”

“…In animal models of drug abuse, the ABA renewal paradigm [whereby the subject is conditioned in one context (A), extinguished in another (B), and is then re-exposed to the original context (A)] emphasizes how environmental contexts that have been associated with drug use can directly prompt reinstatement (LeCocq et al, 2020 ). Clinical research has established that drug-associated contexts promote cue reactivity, elevate craving responses, and are sufficient to elicit context-induced relapse (LeCocq et al, 2020 ). Recent studies have suggested that a way to improve the discovery of more effective treatments is to accentuate the influence of environmental contexts and their influence on drug-seeking behaviors (Everitt and Robbins, 2005 ; Aguilar et al, 2009 ; LeCocq et al, 2020 ).…”

“…Clinical research has established that drug-associated contexts promote cue reactivity, elevate craving responses, and are sufficient to elicit context-induced relapse (LeCocq et al, 2020 ). Recent studies have suggested that a way to improve the discovery of more effective treatments is to accentuate the influence of environmental contexts and their influence on drug-seeking behaviors (Everitt and Robbins, 2005 ; Aguilar et al, 2009 ; LeCocq et al, 2020 ). Therefore, CPP serves as a specialized paradigm that can be exploited just for this purpose.…”

Translational Research in the Neurobiological Mechanisms of Alcohol and Substance Use Disorders

“…In the review by LeCoq et al, the authors discuss in extensive detail the influence of context on drug-seeking behaviors [9]. These contextual factors can take a number of forms including physical environment, social conditions, or interoceptive states induced by drug intake and can significantly influence consumption, subjective drug effects, relapse-like behavior, and drug craving.…”