DESCRIPTION Dopamine (DA) neurons are uniquely vulnerable to damage and cell death, and their loss in humans is associated with diseases including Parkinson's disease (PD). There is a large body of evidence suggesting that the destruction of DA neurons in PD involves the accumulation of free radicals. The antioxidant hormone, melatonin, is one of the most potent endogenous scavengers of oxyradicals yet its ability to rescue, prevent or repair damage to DA neurons has not been directly studied. This proposal seeks to test melatonin's effects on DA neurons in several laboratory models associated with oxidative stress, including growth factor deprivation or neurotoxic injury from MPP+ or 6-OHDA. Preliminary studies reveal a remarkable ability of melatonin to rescue developing and neurotoxin- damaged DA neurons from impending cell death in culture and in vivo and to further promote the growth and regeneration of DA fibers. The ultimate goal of this research is to provide a fuller understanding of the role that melatonin might play in increasing the survival of neurons in the injured DA system and lay a foundation for development of treatments for PD and other diseases with compromised DA systems.