Early in Parkinson's disease (PD) physical activity becomes difficult resulting in a more sedentary lifestyle. Clinical and experimental studies have found that increased activity following striatal dopamine loss leads to increased motor function. Decreased physical activity early in PD along with findings that increased physical activity results in functional improvement suggested to us that decreased physical activity during the period of nigrostriatal degeneration may not only be a symptom of the injury, but may also act to potentiate the degeneration. Using the bilateral MPTP mouse model of PD, we restricted use of one forelimb for the first 7 days post-injection. This transient behavioral manipulation during the period of dopamine degeneration resulted in a long-lasting deficit of the restricted forelimb. This was manifested as sustained asymmetrical use of the forelimbs during wall exploration, as well as a neurochemical imbalance between striatal hemispheres measured by immunoreactivity of the dopamine terminal markers, DAT, VMAT2 and TH. These results show a significant interaction between behavior and neurochemistry and suggest that a reduction in activity level may further exacerbate degeneration.