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). L-DOPA is commonly used to treat Parkinsonian symptoms, but little is known about how it affects presynaptic DA neurotransmission. Using in vivo fast-scan cyclic voltammetry, we show L-DOPA inhibits DA reuptake in a region-specific and dose-dependent manner, and L-DOPA has paradoxical effects on release. These findings may be important when considering mechanisms for L-DOPA's therapeutic benefits and adverse side-effects.
['Harun|Rashed|R|', 'Hare|Kristin M|KM|', 'Brough|Elizabeth M|EM|', 'Munoz|Miranda J|MJ|', 'Grassi|Christine M|CM|', 'Torres|Gonzalo E|GE|', 'Grace|Anthony A|AA|', 'Wagner|Amy K|AK|']
voltammetry dopamine Parkinson's disease striatum dyskinesia levodopa