Grant: Operating Grant

Major depression, a condition affecting 3.2-6% of Canadians and with elevated health care costs, is characterized by depressed mood, anhedonia, weight loss or gain, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue, despair, and/or cognitive impairments. The discovery and validation of new targets for the treatment of depression is of extreme importance, since the available treatments are clinically effective in only one third of the patients and importantly, they can also cause serious side effects. A new promising target for depression seems to be the melatonergic system. In mammals, melatonin acts through MT1 and MT2 receptors and the impact of these receptors on mood disorders, together and separately, is still unknown. The present proposal will combine behavioral, in vivo electrophysiological, molecular biology approaches to investigate the role of MT 1 receptors in the pathogenesis of depression and clarify the mechanism of action. For the first time, a novel cutting-edge selective MT1 agonist (called UCM871), recently synthetized in collaboration with a group of Italian chemists will be tested. The present research will thus validate a novel target for antidepressant drugs, representing an alternative to current therapies.