Abstract
l-dopa is used to treat the motor symptoms associated with Parkinson’s disease, a neurodegenerative movement disorder characterized by a loss of dopamine neurons. l-dopa is the precursor to dopamine and crosses the blood-brain barrier to increase dopamine neurotransmission. This review will focus on the findings that dopamine produced from l-dopa is mediated in part by serotonin neurons. Direct evidence will be provided that increases in dopamine cause oxidative stress and damage serotonin neurons. Similarly, chronic l-dopa produces deficits in serotonin neurotransmission, including decreases in both serotonin cell bodies within the dorsal raphe and serotonin neurotransmitter concentrations in several forebrain regions. Since serotonin is involved in many important physiological processes including mood and cognition, l-dopa induced serotonin deficits may play a role in the side-effect symptoms observed in Parkinson’s disease patients treated with l-dopa.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disorder behindAlzheimer’s, affecting nearly a million people in the United States [1]
The results indicated that L-dopa dose dependently increased extracellular dopamine in all brain regions, and that these effects were abolished when raphe
The MAO type B inhibitor deprenyl, as well as ascorbic acid pretreatment prevented the L-dopa induced loss of 5-HT neurons within the DRN, demonstrating that dopamine degradation and oxidative stress contribute to the L-dopa induced damage to 5-HT systems [17]. These data are consistent with previous work demonstrating that TPH2 expression in the DRN is decreased in rats with bilateral 6-OHDA lesions and exacerbated by chronic L-dopa treatment [56], but are somewhat at variance with human post-mortem studies that did not find differences in DRN Tryptophan hydroxylase (TPH)+ neuron number when comparing dyskinetic to non-dyskinetic PD patients [57]
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disorder behind. Many non-motor symptoms are associated with PD itself, such as depression, anxiety, sleep disorders, and cognitive impairments [10]; all of which greatly impact the overall quality of life of the patient. Some clinical reports suggest that these symptoms are not improved and may be exacerbated by L-dopa treatment [11,12,13]. Both the negative side-effects of L-dopa, as well as the non-motor symptoms of PD may involve the brain serotonin (5-HT) system. This review will summarize the findings that L-dopa can be toxic to central 5-HT neurons and result in 5-HT related deficits that could lead to overall physiological dysfunction in PD patients after chronic L-dopa therapy
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