ArticleJournal of neurochemistry2014
Striatal serotonin 2C receptors decrease nigrostriatal dopamine release by increasing GABA-A receptor tone in the substantia nigra.
Article in Journal of neurochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
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- Synaptic Interactions Between Serotonergic and Dopaminergic Systems in Parkinson's Disease.Current neuropharmacology · 2025Review
- Basolateral Amygdala Serotonin 2C Receptor Regulates Emotional Disorder-Related Symptoms Induced by Chronic Methamphetamine Administration.Frontiers in pharmacology · 2021Article
- Serotonergic Modulation of Nigrostriatal and Mesolimbic Dopamine and Motor/Exploratory Behaviors in the Rat.Frontiers in neuroscience · 2021Article
- Effects of Jian-Pi-Zhi-Dong Decoction on the Expression of 5-HT and Its Receptor in a Rat Model of Tourette Syndrome and Comorbid Anxiety.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Detection of a High-Turnover Serotonin Circuit in the Mouse Brain Using Mass Spectrometry Imaging.iScience · 2019Article
- An Interaction between Serotonin Receptor Signaling and Dopamine Enhances Goal-Directed Vigor and Persistence in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Depression in Parkinson's Disease: The Contribution from Animal Studies.Parkinson's disease · 2017Review
- Serotonin-2C and -2a receptor co-expression on cells in the rat medial prefrontal cortex.Neuroscience · 2015Article
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Drugs acting at the serotonin-2C (5-HT2C) receptor subtype have shown promise as therapeutics in multiple syndromes including obesity, depression, and Parkinson's disease. While it is established that 5-HT2C receptor stimulation inhibits DA release, the neural circuits and the localization of the relevant 5-HT2C receptors remain unknown. This study used dual-probe in vivo microdialysis to investigate the relative contributions of 5-HT2C receptors localized in the rat substantia nigra (SN) and caudate-putamen (CP) in the control of nigrostriatal DA release. Systemic administration (3.0 mg/kg) of the 5-HT2C receptor selective agonist Ro 60-0175 [(αS)-6-Chloro-5-fluoro-α-methyl-1H-indole-1-ethanamine fumarate] decreased, whereas intrastriatal infusions of the selective 5-HT2C antagonist SB 242084 [6-Chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide; 1.0 μM] increased, basal DA in the CP. Depending on the site within the SN pars reticulata (SNpr), infusions of SB 242084 had more modest but significant effects. Moreover, infusions of the GABA-A receptor agonist muscimol (10 μM) into the SNpr completely reversed the increases in striatal DA release produced by intrastriatal infusions of SB 242084. These findings suggest a role for 5-HT2C receptors regulating striatal DA release that is highly localized. 5-HT2C receptors localized in the striatum may represent a primary site of action that is mediated by the actions on GABAergic activity in the SN. Dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) project to the caudate-putamen (CP; striatum). This circuitry is implicated in numerous pathologies including Parkinson's disease. Using in vivo microdialysis, we demonstrated that blockade of serotonin (5-HT) 2C receptors in the CP increased nigrostriatal DA release. Infusions of a GABA-A agonist into the substantia nigra pars reticulata (SNpr) blocked this increase. This work indicates that striatal serotonin 2C receptors regulate GABAergic tone in the SNpr, which in turn regulates nigrostriatal DA release.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.