Recent developments in the behavioural and pharmacological enhancement of extinction of drug seeking

Abstract

One of the principal barriers to overcoming addiction is the propensity to relapse, even after months or years of abstinence. Relapse can be precipitated by cues and contexts associated with drug use; thus, decreasing the conditioned properties of these cues and contexts may assist in preventing relapse. The predictive power of drug cues and contexts can be reduced by repeatedly presenting them in the absence of the drug reinforcer, a process known as extinction. The potential of extinction to limit relapse has generated considerable interest and research over the past few decades. While pre-clinical animal models suggest extinction learning assists relapse prevention, treatment efficacy is often lacking when extinction learning principles are translated into clinical trials. Conklin and Tiffany (Addiction, 2002) suggest the lack of efficacy in clinical practice may be due to limited translation of procedures demonstrated through animal research and propose several methodological improvements to enhance extinction learning for drug addiction. This review will examine recent advances in the behavioural and pharmacological manipulation of extinction learning, based on research from pre-clinical models. In addition, the translation of pre-clinical findings-both those suggested by Conklin and Tiffany () and novel demonstrations from the past 13 years-into clinical trials and the efficacy of these methods in reducing craving and relapse, where available, will be discussed. Finally, we highlight areas where promising pre-clinical models have not yet been integrated into current clinical practice but, if applied, could improve upon existing behavioural and pharmacological methods.

Glucagon-Like Peptide-1 Analog Exendin-4 Ameliorates Cocaine-Mediated Behavior by Inhibiting Toll-Like Receptor 4 Signaling in Mice

“…Extinction training is an active learning process that leads to a gradual decline in acquired response. It generates the new learning and memories that predict no more delivery of addictive drugs, through which the expression of initial memories of addictive drugs to control behavior was suppressed ( Marlatt, 1990 ; Chesworth and Corbit, 2015 ), and thereby reducing the susceptibility of relapse ( Heather and Bradley, 1990 ). However, extinction exposure alone proves insufficient ( Marlatt, 1990 ).…”

Memory Retrieval-Extinction Combined With Virtual Reality Reducing Drug Craving for Methamphetamine: Study Protocol for a Randomized Controlled Trial

“…From a theoretical perspective, VR appears to be a more useful method to reactivate drug-associated memories as drug-associated cues in VR elicit more stronger craving than drug-associated cues in pictures (24) or videos (25,26). Using VR can not only present drug-related paraphernalia in proximal confrontation patterns, but also provide interaction with specific drug-related environment or multi-sensorial stimuli (distal risks), which are known to be the most critical triggers of relapse (58,59). VR might thus offer high-risk methamphetamine-related environments.…”

The Contribution of the Amygdala to Reward-Related Learning and Extinction

“…While a number of studies demonstrate DCS-enhanced extinction learning (reviewed in Refs. [66,67]), it appears the timing of DCS administration is critical in determining whether it enhances or impedes extinction learning (for a discussion, see Ref. [65]).…”