nNOS activity is decreased in the striatum of L-DOPA-treated Parkinson’s disease model

Parkinson’s disease (PD), resulting from the loss of dopaminergic neurons in the basal ganglia, is a devastating neurodegenerative disease that impairs voluntary movement. Currently, the standard treatment for PD aims to replace dopamine via L-DOPA administration. However, this treatment often causes equally debilitating symptoms, termed dyskinesias. cGMP, a messenger molecule that plays a role in neuronal excitability, has recently been noted as a possible target for therapy since levels of cGMP, controlled through degradation by phosphodiesterases and synthesis by nitric oxide (NO) signaling, are depressed during dyskinesias. This study sought to measure the activity of neuronal nitric oxide synthase (nNOS) in a rat model of PD and dyskinesia to determine whether the decrease in cGMP is due to decreased NOdependent-synthesis or increased degradation. We found decreased levels of NO in dyskinetic animals, indicating a decrease in nNOS activity correlating to the decrease in cGMP reporting in other studies.