Project 170676

Monoamine neurotransmitters such as dopamine and serotonin are involved in the regulation of multiple brain functions including movement, mood and reward. Because of this, the biological mechanisms that mediate the action of these neurotransmitters have become major therapeutic targets for the management of neuropsychiatric disorders such as depression, Parkinson disease and schizophrenia that collectively affect large segments of the population. At the cellular level, monoamine neurotransmitters exert their action by stimulating receptors that modulate behavioral responses by initiating cascades of biochemical events-also designated as signaling pathways. Most psychotropic drugs are designed to affect either the level of neurotransmitters or specific subclasses of receptors. However these drugs have a poor specificity of action leading to the development of multiple unwanted side effects. Furthermore, efficient treatment of psychiatric disorders often involves the modulation of more then one neurotransmitter at a time. A better understanding of the regulation of signaling pathways by monoamine neurotransmitters may allow unraveling the interplay between these different neurotransmitter systems. In turn, this could results in the development of better therapeutic agents having lesser side effects. Our work and the work of others have identified molecules from the Akt/GSK3signaling pathway as important mediators of the action of both dopamine and serotonin on behavior. In this project we propose to use an integrated approach involving the biochemical and behavioral characterization in genetically modified animals models to decipher the role of these signaling pathways in the regulation of brain functions.

using genetically modified animal models to study the role of specific signaling pathways in neuropsychiatric disorders