ArticleMolecular psychiatry2020
5-HT2C receptor blockade reverses SSRI-associated basal ganglia dysfunction and potentiates therapeutic efficacy.
Article in Molecular psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 50 citations in OpenAlex.
- A nuclei-specific fronto-amygdala pathway and its neurotransmitter receptor distribution: Implications for Antidepressant Selection.Molecular psychiatry · 2026Article
- 5-HT2C receptors in the glutamatergic neurons of dorsal raphe nucleus orchestrate the comorbidity of pain and anxiety in mice.BMC medicine · 2026Article
- The Complex Role of Serotonin-Dopamine-Glutamate Receptors in Major Depression.Advances in experimental medicine and biology · 2026Review
- Mechanistic intersections between migraine and major depressive disorder.The journal of headache and pain · 2025Review
- DRN-SNc serotonergic circuit drives stress-induced motor deficits and Parkinson's disease vulnerability.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Does Dysregulation Of The Indirect Pathway Contribute To The Pathophysiology Of Catatonia Through Neurotransmitter Imbalance?Clinical neuropsychiatry · 2025Article
- Intestinal Epithelial Serotonin as a Novel Target for Treating Disorders of Gut-Brain Interaction and Mood.Gastroenterology · 2025Article
- Role ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Greater Apathy Associated With Selective Serotonin Reuptake Inhibitor Use in Parkinson's Disease.Journal of geriatric psychiatry and neurology · 2025Article
- Sexual Dysfunction Induced by Antidepressants-A Pharmacovigilance Study Using Data from VigiBasePharmaceuticals (Basel, Switzerland) · 2024Article
- Estrogen-immuno-neuromodulation disorders in menopausal depression.Journal of neuroinflammation · 2024Review
- Calcium and Neural Stem Cell Proliferation.International journal of molecular sciences · 2024Review
- Influence ofCanadian journal of psychiatry. Revue canadienne de psychiatrie · 2024Article
- Article
- Dopamine transporter blockade during adolescence increases adult dopamine function, impulsivity, and aggression.Molecular psychiatry · 2023Article
- Agomelatine: a potential novel approach for the treatment of memory disorder in neurodegenerative disease.Neural regeneration research · 2023Review
- Integrative multi-omics landscape of fluoxetine action across 27 brain regions reveals global increase in energy metabolism and region-specific chromatin remodelling.Molecular psychiatry · 2022Article
- Disturbance of neurotransmitter metabolism in drug-naïve, first-episode major depressive disorder: a comparative study on adult and adolescent cohorts.European archives of psychiatry and clinical neuroscience · 2022Article
- The Implication of 5-HT Receptor Family Members in Aggression, Depression and Suicide: Similarity and Difference.International journal of molecular sciences · 2022Review
- Effect of Modified Yukmijihwang-Tang on Sleep Quality in the Rat.Clocks & sleep · 2022Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Serotonin (5-HT) selective reuptake inhibitors (SSRIs) are widely used in the treatment of depression and anxiety disorders, but responsiveness is uncertain and side effects often lead to discontinuation. Side effect profiles suggest that SSRIs reduce dopaminergic (DAergic) activity, but specific mechanistic insight is missing. Here we show in mice that SSRIs impair motor function by acting on 5-HT2C receptors in the substantia nigra pars reticulata (SNr), which in turn inhibits nigra pars compacta (SNc) DAergic neurons. SSRI-induced motor deficits can be reversed by systemic or SNr-localized 5-HT2C receptor antagonism. SSRIs induce SNr hyperactivity and SNc hypoactivity that can also be reversed by systemic 5-HT2C receptor antagonism. Optogenetic inhibition of SNc DAergic neurons mimics the motor deficits due to chronic SSRI treatment, whereas local SNr 5-HT2C receptor antagonism or optogenetic activation of SNc DAergic neurons reverse SSRI-induced motor deficits. Lastly, we find that 5-HT2C receptor antagonism potentiates the antidepressant and anxiolytic effects of SSRIs. Together our findings demonstrate opposing roles for 5-HT2C receptors in the effects of SSRIs on motor function and affective behavior, highlighting the potential benefits of 5-HT2C receptor antagonists for both reduction of motor side effects of SSRIs and augmentation of therapeutic antidepressant and anxiolytic effects.
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Registered trials
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.