Targeting extinction and reconsolidation mechanisms to combat the impact of drug cues on addiction.

Drug addiction is a progressive and compulsive disorder, where recurrent craving and relapse to drug-seeking occur even after long periods of abstinence. A major contributing factor to relapse is drug-associated cues. Here we review behavioral and pharmacological studies outlining novel methods of effective and persistent reductions in cue-induced relapse behavior in animal models. We focus on extinction and reconsolidation of cue-drug associations as the memory processes that are the most likely targets for interventions. Extinction involves the formation of new inhibitory memories rather than memory erasure; thus, it should be possible to facilitate the extinction of cue-drug memories to reduce relapse. We propose that context-dependency of extinction might be altered by mnemonic agents, thereby enhancing the efficacy of cue-exposure therapy as treatment strategy. In contrast, interfering with memory reconsolidation processes can disrupt the integrity or strength of specific cue-drug memories. Reconsolidation is argued to be a distinct process that occurs over a brief time period after memory is reactivated/retrieved - when the memory becomes labile and vulnerable to disruption. Reconsolidation is thought to be an independent, perhaps opposing, process to extinction and disruption of reconsolidation has recently been shown to directly affect subsequent cue-drug memory retrieval in an animal model of relapse. We hypothesize that a combined approach aimed at both enhancing the consolidation of cue-drug extinction and interfering with the reconsolidation of cue-drug memories will have a greater potential for persistently inhibiting cue-induced relapse than either treatment alone.