Fast‐scan cyclic voltammetry demonstrates that L‐DOPA produces dose‐dependent, regionally selective bimodal effects on striatal dopamine kinetics in vivo

Parkinson's disease (PD) is a debilitating condition that is caused by a relatively specific degeneration of dopaminergic (DAergic) neurons of the substantia nigra pars compacta. L‐DOPA was introduced as a viable treatment option for PD over 40 years ago and still remains the most common and effective therapy for PD. Though the effects of L‐DOPA to augment striatal DA production are well known, little is actually known about how L‐DOPA alters the kinetics of DA neurotransmission that contribute to its beneficial and adverse effects. In this study, we examined the effects of L‐DOPA administration (50 mg/kg carbidopa + 0, 100, and 250 mg/kg L‐DOPA) on regional electrically stimulated DA response kinetics using fast‐scan cyclic voltammetry in anesthetized rats. We demonstrate that L‐DOPA enhances DA release in both the dorsal striatum (D‐STR) and nucleus accumbens (NAc), but surprisingly causes a delayed inhibition of release in the D‐STR. In both regions, L‐DOPA progressively attenuated reuptake kinetics, predominantly through a decrease in Vmax. These findings have important implications on understanding the pharmacodynamics of L‐DOPA, which may be informative for understanding its therapeutic effects and also common side effects like L‐DOPA‐induced dyskinesias (LID).