Grant: CIHR Fellowship

Cigarette smoking is an addiction that is the most preventable cause of premature death in the world. Approximately 90% of adult smokers initiate tobacco use before age 18, and this early behaviour could be critical to addiction. There is evidence that early exposure to nicotine, the addictive component of tobacco, can affect immediate behaviours but more interestingly can have persistent effects on behaviour long after nicotine exposure. Nicotine has also been shown to induce gene expression changes in an age-related manner. One possible explanation for nicotine induced changes in behaviour and gene expression could be a result of epigenetic modifications. Epigenetic modifications are changes that lead to structural remodeling of the genetic material without altering the DNA sequence and can result in gene expression alterations. In fact, recent evidence indicates that nicotine exposure can induce epigenetic modifications which could explain immediate and persistent changes involved in the addiction process. To study some aspects addiction, mouse models provide excellent research tools as they are available on defined genetic backgrounds and because environmental factors can be well-controlled. In this system, the effect of nicotine exposure can be systematically assessed in an age dependent manner for gene expression changes, the role of epigenetic modifications, and behavioural modifications by controlling the environmental factor (nicotine) in genetically identical mice at varying adolescent ages and at adulthood. We propose nicotine exposure will have dramatic age-related behavioural, epigenetic and transcriptomic changes in regions of the brain involved in reward. Identifying these changes will provide unique insight into the effects of age-related nicotine exposure on gene expression, the underlying mechanisms mediated by epigenetics, and behavioural alterations, thereby suggesting possibilities about how we may intervene in the addiction process.