Grant: CIHR Fellowship

Drug addiction is a serious health issue in Canada and throughout the world. A major goal of addiction research has been to identify the circuit-level changes in activity caused by drugs of abuse that 'hijack' the normal processes underlying reward learning in the brain, leading to compulsive drug-seeking behaviour. Key pathways implicated in addiction are the projections from dopaminergic (DA) neurons in the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). The release of dopamine from these projections is increased by drugs of abuse such as cocaine, but direct observation of native neural activity within these pathways has remained elusive. The recently developed 'fiber photometry' technique now allows for optical recording of specific neural projection pathways within the brains of awake, behaving animals. In the present study, we propose to use fiber photometry to analyze changes in the activity of DA projections to the NAc and mPFc during different forms of cocaine-mediated reward learning. This approach will allow us to elucidate circuit-level alterations in the reward pathway of the brain which underlie behavioural changes induced by cocaine. We will also be able to identify causal patterns of activity that precede the initiation of drug-seeking behaviours, a potentially crucial aspect of addiction in humans. The results from this study will therefore be of broad interest both to neuroscience researchers and to clinicians studying the effects of cocaine on the brain, and have the potential to inform future therapeutic strategies for drug abuse.