Behavioral and fMRI analysis of functional recovery in Parkinsonian animals

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Trophic factor treatment offers a promising approach for ameliorating the injury and loss of dopamine neurons in Parkinson's disease. However, safe and efficacious methods for delivering trophic factors into the brain with minimal side effects need to be developed in order for this approach to be successful. In this project we test the concept of using programmable pumps for the controlled, site-specific delivery of trophic factors. Medtronic pumps are used to test the hypothesis that the chronic intracerebral infusion of GDNF stimulates functional recovery of the nigrostriatal dopamine system. Project 2 has two goals. The first is to quantify the changes in parkinsonian features accompanying chronic GDNF infusion into the lateral ventricle and the putamen. Bradykinesia, rigidity, posture, balance and tremor will be rated from standardized videotaped tests of movement functions. Coarse and fine motor movement times will be quantified using an automated Movement Assessment Panel. The second goal is to utilize functional magnetic resonance imaging (fMRI) to noninvasively follow functional changes in the nigrostriatal dopamine system in aminals showing behavioral recovery from chronic GDNF infusion. Amphetamine-induced stimulation of dopaminergic processes in the caudate nucleus, putamen and substantia nigra will be mapped by fMRI as animals undergo behavioral recovery.