Grant: Project Grant

Drug addictions are amongst the most prevalent and fatal disorders in the world. In Canada, cocaine is the most used illicit drug, and there are no approved medications for cocaine addiction. A major clinical challenge is the high rate of relapse during abstinence. Users are especially vulnerable to cues associated with drug use. By eliciting drug craving, these cues promote relapse. To develop interventions, we must understand how drug cues influence brain and behaviour. Animal models are on the front lines to achieve this goal because they allow precise control over drug use and environment. Animal models of relapse have often focused on the effects of a type of drug cue termed 'conditioned stimulus'. Typically, a rat presses a lever for a drug infusion, and a discrete cue (e.g., a light; the conditioned stimulus) accompanies the infusion. That is, the conditioned stimulus and the brain mechanisms it recruits operate after drug seeking is initiated and come as a consequence rather than a trigger. However, relapse also involves cues that precede (i.e., elicit) drug-seeking actions, and that signal when drug is available. These are discriminative stimuli, and they are a unique class of cues, because they control drug seeking before and during relapse. How discriminative stimuli may influence cocaine relapse, and the underlying brain mechanisms are largely unknown. We will address this here by examining the persistence of relapse triggered by cocaine-associated discriminative stimuli during abstinence, and the contributions of 1) the chemical messenger glutamate, which mediates the effects of cues on psychology and behaviour, and 2) activity in neural circuits involving brain regions with critical roles in processing reward cues. We expect to make key discoveries on the behavioural and brain mechanisms of cocaine relapse. This in turn will be important in determining directions for new interventions to manage drug addiction.