ArticleMolecular psychiatry2012
Organic cation transporter 2 controls brain norepinephrine and serotonin clearance and antidepressant response.
Article in Molecular psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 148 citations in OpenAlex.
- Organic cation transporter variation and response to smoking cessation therapies.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2014Trial
- Gabapentin CNS exposure and analgesic response are modulated by OCT2 genotype in patients with chronic neuropathic pain.Frontiers in pharmacology · 2026Article
- Signaling by intracellular βCell reports · 2025Article
- Serotonin regulates in a cell-type specific manner light-evoked response and synaptic activity in mouse retinal ganglion cells.Biological research · 2025Article
- The identification of adenylyl cyclase modulators as potential receptors for 6-nitrodopamine in human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and their relevance in heart inotropism.Frontiers in pharmacology · 2025Article
- Decoding serotonin: the molecular symphony behind depression.Frontiers in cellular neuroscience · 2025Review
- Role of Serotonylation and SERT Posttranslational Modifications in Alzheimer's Disease Pathogenesis.Aging and disease · 2024Review
- G protein-biased LPAR1 agonism of prototypic antidepressants: Implication in the identification of novel therapeutic target for depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Organic cation transporters in psychiatric and substance use disorders.Pharmacology & therapeutics · 2024Review
- Heterotypic Stressors Unmask Behavioral Influences of PMAT Deficiency in Mice.International journal of molecular sciences · 2023Article
- Heterotypic stressors unmask behavioral influences of PMAT deficiency in mice.bioRxiv : the preprint server for biology · 2023Article
- Summarizing studies using constitutive genetic deficiency to investigate behavioural influences of uptake 2 monoamine transporters.Basic & clinical pharmacology & toxicology · 2023Review
- Organic cation transporter 2 contributes to SSRI antidepressant efficacy by controlling tryptophan availability in the brain.Translational psychiatry · 2023Article
- Maternal Immune Activation Induces Cortical Catecholaminergic Hypofunction and Cognitive Impairments in Offspring.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- Cell type-specific NRBF2 orchestrates autophagic flux and adult hippocampal neurogenesis in chronic stress-induced depression.Cell discovery · 2023Article
- Molecular basis of polyspecific drug and xenobiotic recognition by OCT1 and OCT2.Nature structural & molecular biology · 2023Article
- Enriched environmental exposure reduces the onset of action of the serotonin norepinephrin reuptake inhibitor venlafaxine through its effect on parvalbumin interneurons plasticity in mice.Translational psychiatry · 2023Article
- Investigation on the positive chronotropic action of 6-nitrodopamine in the rat isolated atria.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Molecular basis of polyspecific drug binding and transport by OCT1 and OCT2.bioRxiv : the preprint server for biology · 2023Article
- Dolutegravir Discontinuation for Neuropsychiatric Symptoms in People Living with HIV and Their Outcomes after Treatment Change: A Pharmacogenetic Study.Metabolites · 2022Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High-affinity transporters for norepinephrine (NE) and serotonin (5-HT), which ensure neurotransmitter clearance at the synapse, are the principal targets of widely used antidepressant drugs. Antidepressants targeting these high-affinity transporters, however, do not provide positive treatment outcomes for all patients. Other monoamine transport systems, with lower affinity, have been detected in the brain, but their role is largely unknown. Here we report that OCT2, a member of the polyspecific organic cation transporter (OCT) family, is expressed notably in the limbic system and implicated in anxiety and depression-related behaviors in the mouse. Genetic deletion of OCT2 in mice produced a significant reduction in brain tissue concentrations of NE and 5-HT and in ex vivo uptake of both these neurotransmitters in the presence of the dual 5-HT-NE transport blocker, venlafaxine. In vivo clearance of NE and 5-HT evaluated using microiontophoretic electrophysiology was diminished in the hippocampus of OCT2(-/-) mice in the presence of venlafaxine, thereby affecting postsynaptic neuronal activity. OCT2(-/-) mice displayed an altered sensitivity to acute treatments with NE- and/or 5-HT-selective transport blockers in the forced-swim test. Moreover, the mutant mice were insensitive to long-term venlafaxine treatment in a more realistic, corticosterone-induced, chronic depression model. Our findings identify OCT2 as an important postsynaptic determinant of aminergic tonus and mood-related behaviors and a potential pharmacological target for mood disorders therapy.
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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.