Simultaneous Measurement of Striatal Dopamine and Hydrogen Peroxide Transients Associated with L-DOPA Induced...

Parkinson's disease (PD) is a neurodegenerative disorder commonly treated with levodopa (L-DOPA), which eventually induces abnormal involuntary movements (AIMs). The neurochemical contributors to these dyskinesias are unknown; however, several lines of evidence indicate an interplay of dopamine (DA) and oxidative stress. Here, DA and hydrogen peroxide (H₂O₂) were simultaneously monitored at discrete recording sites in the dorsal striata of hemiparkinsonian rats using fast-scan cyclic voltammetry. Mass spectrometry imaging validated the lesions. Hemiparkinsonian rats exhibited classic L-DOPA-induced AIMs and rotations as well as increased DA and H₂O₂ tone over saline controls after 1 week of treatment. By week 3, DA tone remained elevated beyond that of controls, but H₂O₂ tone was largely normalized. At this time point, rapid chemical transients were time-locked with spontaneous bouts of rotation. Striatal H₂O₂ rapidly increased with the initiation of contraversive rotational behaviors in lesioned L-DOPA animals, in both hemispheres. DA signals simultaneously decreased with rotation onset. The results support a role for these striatal neuromodulators in the adaptive changes that occur with L-DOPA treatment in PD and reveal a precise interplay between DA and H₂O₂ in the initiation of involuntary locomotion.