The long-term objective of this research is to explore the therapeutic effects of complex sensorimotor enrichment (exercise) and medication on sensorimotor function in a rat model of early Parkinson's disease (PD) as a translational approach to accelerate the impact for treatment in human PD. Despite the behavioral and neurochemical evidence in both human and animal models, people with PD are rarely referred to exercise/sensorimotor rehabilitation immediately upon diagnosis. As a result, the opportunity to protect the remaining viable dopamine neurons and slow the progression of motor symptoms is lost. Upon diagnosis, the primary form of intervention is the introduction of pharmacotherapy, primarily levodopa. However, in the early stages of PD, administration of levodopa is controversial. Further, the effects of levodopa on the potential benefits of early exercise are unknown. This application reflects a unique study to address the therapeutic effects of early exercise and to examine the role of dopamine-augmenting drugs on functional outcomes in speech and voice (vocalization) in an animal model. A rat model of early PD will be employed to test the effects of dopamine depletion on Ultrasonic Vocalization (rat analogue of voice/speech sensorimotor control). Rats will be tested in a control condition, immediately after neurotoxin exposure (PD model), and after vocal exercise (therapy) with and without levodopa. Changes in rat Ultrasonic Vocalization acoustic parameters and dopamine sparing will be measured as an index of disease severity and functional improvement after exercise or pharmacological treatment. Relevance: This research is will accelerate the acquisition of the neurobiological and behavioral evidence needed to convince both clinical and basic science communities of the legitimate therapeutic value of early repetitive sensorimotor enrichment to slow disease progression in human PD. Further, it is to provide a foundation that will lead to a well-controlled study of the effects of levodopa with and without exercise in an animal model. This will create a translational model for addressing benefits/confounds in early administration of dopamine-augmenting medications in humans. Plain-Language Research Questions: Does exercise (voice therapy) slow the progression of early Parkinson Disease and improve overall functional outcomes? Do anti-Parkinson medications help or interfere with this process?
