Rôle des récepteurs de la netrine-1 dans le développement des systèmes dopaminergiques

 

Cecilia Flores-Parkman Noriega

Institut universitaire en santé mentale Douglas

 

Domaine : neurosciences, santé mentale et toxicomanie

Programme chercheurs-boursiers - Senior

Concours 2014-2015

Compelling evidence indicates that individuals who initiate drug use during adolescence are at a higher risk of developing drug addiction than those who begin drug use during adulthood. Not surprisingly, ongoing efforts are placed to develop prevention and treatment programs during early life. However, the implementation of these strategies has been limited by the lack of knowledge regarding the processes that are ongoing in the adolescent brain and how drugs of abuse may impact on these events. During adolescence, several brain systems involved in mediating the rewarding effects of drugs of abuse are still immature.

Thus, it is likely that exposure to drugs of abuse during adolescence disrupts the normal developmental course of these systems. This disruption may cause an increase in sensitivity to the rewarding effects of drugs of abuse, thereby putting individuals at a higher risk of developing drug addiction. The present proposal is concerned with identifying molecular processes that are key in the development of reward-relevant circuitries during adolescence and that may be a target of drugs of abuse in this early period of life.

Specifically, I will examine whether drugs of abuse during adolescence alter the function of the protein DCC and in turn change the developmental course and adult function of dopamine systems. DCC is a protein involved in neuronal connectivity and is required for the organization of dopamine systems selectively during adolescence. Furthermore, DCC function in dopamine neurons is downregulated by drugs of abuse in early adolescence, but not in adulthood.