Project 173713

Tobacco addiction through cigarette smoking is the leading preventable cause of death in the world. It has become clear that tobacco addiction is the deadliest and kills nearly 4 million people annually. The smoking addiction is particularly frequent in patients suffering from mental health disorders. However, the neurobiological mechanisms that could explain this frequent co-morbidity remain unclear. (DISC1) Disrupted-in-schizophrenia 1 (DISC1) has been identifies as a strong candidate susceptibility gene for major mental illness, including schizophrenia, bipolar disorder, and major depression. We hypothesize that the DISC1 gene is also a risk genetic factor for explaining the co-morbidity between mental health disorders and smoking addiction although its role in tobacco dependence has not been explored so far. Nicotine has been identified as a major psychoactive component of tobacco. Here, we are planning to use intravenous nicotine self-administration (the 'Gold Standard' in the field) in genetically mutant mice as a model to explore the involvement of DISC1 gene in behavioural and brain mechanisms that lead to tobacco dependence and relapse disorders. In collaboration with distinguished scientists in the field, we will perform genetic analysis using clinical blood samples to validate our preclinical findings. By identifying DISC1 as a potential risk gene involved in tobacco addiction, these studies may allow explain the frequent co-morbidity that exists between tobacco dependence and mental health disorders, and develop new therapies against tobacco addiction.