ArticleThe Journal of pharmacology and experimental therapeutics2014
Chronic L-dopa decreases serotonin neurons in a subregion of the dorsal raphe nucleus.
Article in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 43 citations in OpenAlex.
- 5-HTThe Journal of physiology · 2025Article
- Striatal serotonin transporter gain-of-function in L-DOPA-treated, hemi-parkinsonian rats.Brain research · 2023Article
- Current Knowledge on the Background, Pathophysiology and Treatment of Levodopa-Induced Dyskinesia-Literature Review.Journal of clinical medicine · 2021Review
- The effect of 5-HTBritish journal of pharmacology · 2021Article
- Repeated crack cocaine administration alters panic-related responses and delta FosB immunoreactivity in panic-modulating brain regions.Experimental brain research · 2021Article
- Oxidative Stress and Cognitive Decline: The Neuroprotective Role of Natural Antioxidants.Frontiers in neuroscience · 2021Review
- Circuit Mechanisms of L-DOPA-Induced Dyskinesia (LID).Frontiers in neuroscience · 2021Review
- High-resolution PET imaging reveals subtle impairment of the serotonin transporter in an early non-depressed Parkinson's disease cohort.European journal of nuclear medicine and molecular imaging · 2020Article
- L-DOPA in Parkinson's Disease: Looking at the "False" Neurotransmitters and Their Meaning.International journal of molecular sciences · 2019Review
- Impairment of Serotonergic Transmission by the Antiparkinsonian Drug L-DOPA: Mechanisms and Clinical Implications.Frontiers in cellular neuroscience · 2017Review
- The acute and long-term L-DOPA effects are independent from changes in the activity of dorsal raphe serotonergic neurons in 6-OHDA lesioned rats.British journal of pharmacology · 2016Article
- Monoaminergic and Histaminergic Strategies and Treatments in Brain Diseases.Frontiers in neuroscience · 2016Review
- Behavioral impairments and serotonin reductions in rats after chronic L-dopa.Psychopharmacology · 2015Article
- Article
- L-Dopa and Brain Serotonin System Dysfunction.Toxics · 2015Review
- Parkinson's disease-associated melanin steal.Neuropsychiatric disease and treatment · 2014Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
L-Dopa (l-3,4-dihydroxyphenylalanine) is the precursor to dopamine and has become the mainstay therapeutic treatment for Parkinson's disease. Chronic L-dopa is administered to recover motor function in Parkinson's disease patients. However, drug efficacy decreases over time, and debilitating side effects occur, such as dyskinesia and mood disturbances. The therapeutic effect and some of the side effects of L-dopa have been credited to its effect on serotonin (5-HT) neurons. Given these findings, it was hypothesized that chronic L-dopa treatment decreases 5-HT neurons in the dorsal raphe nucleus (DRN) and the content of 5-HT in forebrain regions in a manner that is mediated by oxidative stress. Rats were treated chronically with l-dopa (6 mg/kg; twice daily) for 10 days. Results indicated that the number of 5-HT neurons was significantly decreased in the DRN after l-dopa treatment compared with vehicle. This effect was more pronounced in the caudal-extent of the dorsal DRN, a subregion found to have a significantly higher increase in the 3,4-dihydroxyphenylacetic acid/dopamine ratio in response to acute L-dopa treatment. Furthermore, pretreatment with ascorbic acid (400 mg/kg) or deprenyl (2 mg/kg) prevented the l-dopa-induced decreases in 5-HT neurons. In addition, 5-HT content was decreased significantly in the DRN and prefrontal cortex by l-dopa treatment, effects that were prevented by ascorbic acid pretreatment. Taken together, these data illustrate that chronic L-dopa causes a 5-HT neuron loss and the depletion of 5-HT content in a subregion of the DRN as well as in the frontal cortex through an oxidative-stress mechanism.
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