Grant: Operating Grant

Schizophrenia, major depression, anxiety disorders and drug addiction are among major mental health diseases that are associated to abnormal functions of deep brain regions that belong to a neuronal network that we call the "limbic system". Pharmacological treatments used to date to reduce and control emotional and motivational symptoms that characterize these disorders target neurochemical communications within the limbic network. For instance, abnormal limbic dopamine neurotransmission is associated with psychosis and drug addiction and the current medications target this neurotransmitter. But the limbic network is highly complex and dopamine is obviously not the sole relevant neurochemical messenger involved. Results from previous reseach show that neurotensin, a peptide (small protein-like) that modulates neurotransmission with several limbic regions plays a key role in psychosis and vulnerability to drug addiction. We propose to use complementary multi-technical approaches to further understand the modulation of limbic neurotransmission by neurotensin. Studies are designed to investigate the mechanisms by which this peptide initiates sensitization to the stimulant and the rewarding effect of amphetamine; we will attempt to determine its site of action, its interaction with other neurochemical messengers such as dopamine, glutamate and GABA and the intracellular events that are triggered within neurons of the limbic system by the action of neurotensin. The use of complementary technical approachs is a promising avenue to reveal mechanisms that subserve funtional changes in the brain that lead to abnormal mental states like psychosis and addiction.