This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Dystonia is a devastating movement disorder, characterized by sustained involuntary muscle contractions involving the limbs or the trunk. Dystonia may involve loss of the neurotransmitter dopamine in the brain. Studies in humans and animals suggest that the effects of dopamine depletion may be age-dependent. While dopamine loss typically results in Parkinsonism in older individuals, it may manifest as dystonia at a younger age. Our studies investigate the concept that dopamine depletion early in life results in dystonia, with a series of behavioral experiments that explore the effects of the dopaminergic neurotoxin MPTP in young Rhesus monkeys. In adult Rhesus monkeys, treatment with MPTP produces a classic model of Parkinsonism while it is believed the treatments will induce dystonia instead in the young monkeys. The availability of a primate model of stable and persistent dystonia gives us insight into the pathophysiology of the disorder and makes it possible to study more about the anatomic changes that underlie forms of dystonia that are related to dopamine depletion in humans.
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