Any model of drug addiction needs to explain i) the process by which drug taking in certain individuals develops into compulsive patterns of drug-seeking and drug-taking, and ii) the inability to cease drug-taking, that is, the problem of relapse. Substantial progress has been made such that we now know a great deal about the neurochemical, cellular, molecular, and structural correlates of drug use. Nevertheless, the phenomenon of addiction remains poorly understood. In recent years, there has been a growing interest in the possibility that environmental stimuli or events associated with drug taking may acquire motivational properties and potentiate drug abuse development and relapse. As noted by Falk [24], the effects of drugs are determined not by their pharmacological properties, but more so by ?a cluster of interactions among the pharmacological substance, the set of the organism, and the environmental setting? (p.1503). The first aim of this application is to use a simple animal model to study how psychostimulant drugs and environmental factors interact to persistently alter reward mechanisms and promote compulsive drug seeking behaviour. This research is proposed to extend previous studies by the applicant and colleagues demonstrating that environmental conditions in which drugs are administered modulate a form of drug-induced plasticity known as behavioural sensitisation. In our previous studies, however, sensitisation was determined by quantifying the psychomotor activating effects of drugs and the extent to which drug-environment interactions produce long term alterations in drug reward processes remains unknown. The second aim of this application is to extend previous work by the applicant showing that environmental conditions can profoundly modulate reinstatement of drug seeking (a model of relapse) following abstinence. Therefore, we propose to further investigate, both at a behavioural and systems neuroscience level, these environmental influences in relapse to drug seeking.

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