Grant: Operating Grant

Dopamine is an important neurotransmitter. It modulates various activity including, locomotion, motivated behaviors and neuroendocrine processes. Antipsychotic drugs are used to alleviate schizophrenia symptoms and share the common property to interact with dopamine receptors. But, their cellular and molecular mechanisms of action remain poorly understood. In recent years, we have identified an important role for transcription factors of the nuclear receptor family Nur77 and retinoid X receptor (RXR) in the action of dopaminergique drugs. In the present proposal we would like 1) to demonstrate the formation of the transcriptional complex Nur77/RXR following antipsychotic drug administration; 2) to identify gene targets of Nur77/RXR transcriptional activity in antipsychotic drug-induced gene expression; and 3) to evaluate the putative functional effect of a single nucleotide polymorphism (SNP) in the human Nur77 messenger RNA. Data generate from these experiments should improve our understanding on the role of Nur77 and RXR in antipsychotic drug effects. Since Nur77 and RXR are associated with maintenance of homeostatic dopamine activity and potential beneficial effects against antipsychotic drug-induced side effects, targeting Nur77/RXR transcriptional activity might represent a new way to ameliorate dopamine related disorder treatments. Characterization of the Nur77 SNP may help to predict individuals with higher risk to develop dopamine drug side effects leading to a better and more individualize therapeutic approach.