The effect of dopamine on MPTP-induced rotarod disability

Dopamine depletion in Parkinson's disease (PD) results in bradykinesia and tremor. Therapeutic administration of the dopamine precursor, l-Dopa, alleviates these symptoms but dyskinesia's can manifest with chronic treatment. In the MPTP toxin mouse model of PD, lesion severity is often assessed by the rotarod behavioral assay. Dopamine depletion by MPTP is thought to induce rotarod behavioral decline. Here we surveyed rotarod behavior and striatal dopamine at timed intervals post-MPTP. Paradoxically, rotarod disability coincided with gradual striatal dopamine restoration. l-Dopa supplementation exacerbated rotarod disability, whereas dopamine antagonism restored performance. Conclusion: dopamine restoration, not depletion, precipitates rotarod disability after MPTP intoxication, and caution should be applied when using this assay for MPTP.