Role of cues and contexts on drug-seeking behaviour

Abstract

Environmental stimuli are powerful mediators of craving and relapse in substance-abuse disorders. This review examined how animal models have been used to investigate the cognitive mechanisms through which cues are able to affect drug-seeking behaviour. We address how animal models can describe the way drug-associated cues come to facilitate the development and persistence of drug taking, as well as how these cues are critical to the tendency to relapse that characterizes substance-abuse disorders. Drug-associated cues acquire properties of conditioned reinforcement, incentive motivation and discriminative control, which allow them to influence drug-seeking behaviour. Using these models, researchers have been able to investigate the pharmacology subserving the behavioural impact of environmental stimuli, some of which we highlight. Subsequently, we examine whether the impact of drug-associated stimuli can be attenuated via a process of extinction, and how this question is addressed in the laboratory. We discuss how preclinical research has been translated into behavioural therapies targeting substance abuse, as well as highlight potential developments to therapies that might produce more enduring changes in behaviour.

Figure 1

Animal models for cue-induced drug taking and drug seeking. Panel A shows preparation used to study drug taking. These are variations of the self-administration model, designed specifically to examine the effect of cue on drug taking. In conditioned reinforcement, a response-contingent cue comes to possess reinforcing effects, and is able to enhance drug taking and support acquisition of a new response. In discriminative control, a cue that signals availability of drug promotes responding (in the presence or absence of further drug reinforcement), while a cue that signals availability of saline or water inhibits responding. Panel B shows preparations used to study relapse to drug seeking. In cue-induced reinstatement, the response is extinguished in the absence of the cue, and then recovered by re-pairing the cue with the drug-seeking instrumental response. In context-induced reinstatement, the response is extinguished in a distinctively different context from that used for self-administration, and recovered by re-exposure to that original drug-taking context. In incubation of craving, rats are subjected to a period of enforced abstinence, but with no further behavioural training. Cues are subsequently able to support responding even in the absence of further drug reinforcement. Typically, there is an increase in cue-induced drug seeking after a period of abstinence. It should be noted that both conditioned reinforcers and discriminative cues (Panel A) are able to produce drug seeking after extinction or withdrawal (Panel B).

Figure 2

Different extinction protocols leading to a change in drug seeking. All of these represent variants of the extinction-reinstatement model (Figure 1B), which allow researchers to examine the effect of extinguishing drug-associated environmental stimuli on subsequent drug-seeking behaviour.