ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Striatal dopamine release and genetic variation of the serotonin 2C receptor in humans.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Genetic variation and dopamine D2 receptor availability: a systematic review and meta-analysis of human in vivo molecular imaging studies.Translational psychiatry · 2016Pooled it
- Neurotransmitter and metabolic effects of interferon-alpha in association with decreased striatal dopamine in a non-human primate model of cytokine-Induced depression.Brain, behavior, and immunity · 2025Article
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- Biological function and clinical application prospect of tsRNAs in digestive system biology and pathology.Cell communication and signaling : CCS · 2023Review
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- Serotonin 5-HTScientific reports · 2019Article
- Association of SerotoninFrontiers in psychiatry · 2019Article
- 5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- The activity of the serotonin receptor 2C is regulated by alternative splicing.Human genetics · 2017Review
- New Repeat Polymorphism in theThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Serotonin-Related Gene Variants in Patients with Irritable Bowel Syndrome and Depressive or Anxiety Disorders.Gastroenterology research and practice · 2017Article
- Persistent neuropathic pain increases synaptic GluA1 subunit levels in core and shell subregions of the nucleus accumbens.Neuroscience letters · 2015Article
- Frontostriatal Gating of Tinnitus and Chronic Pain.Trends in cognitive sciences · 2015Review
- Genetic Polymorphisms in the Dopamine Receptor 2 Predict Acute Pain Severity After Motor Vehicle Collision.The Clinical journal of pain · 2015Article
- Persistent pain alters AMPA receptor subunit levels in the nucleus accumbens.Molecular brain · 2015Article
- Striatal Hypersensitivity During Stress in Remitted Individuals with Recurrent Depression.Biological psychiatry · 2015Article
- Mice Lacking Serotonin 2C Receptors Have increased Affective Responses to Aversive Stimuli.PloS one · 2015Article
- Serotonin 5-HT2 receptor interactions with dopamine function: implications for therapeutics in cocaine use disorder.Pharmacological reviews · 2015Review
- Variation within the serotonin (5-HT) 5-HT₂C receptor system aligns with vulnerability to cocaine cue reactivity.Translational psychiatry · 2014Article
- Insights into the influence of 5-HT2c aminoacidic variants with the inhibitory action of serotonin inverse agonists and antagonists.Journal of molecular modeling · 2014Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Mesoaccumbal and nigrostriatal projections are sensitive to stress, and heightened stress sensitivity is thought to confer risk for neuropsychiatric disorders. Serotonin 2C (5-HT(2C)) receptors mediate the inhibitory effects of serotonin on dopaminergic circuitry in experimental animals, and preclinical findings have implicated 5-HT(2C) receptors in motivated behaviors and psychotropic drug mechanisms. In humans, a common missense single-nucleotide change (rs6318, Cys23Ser) in the 5-HT(2C) receptor gene (HTR2C) has been associated with altered activity in vitro and with clinical mood disorders. We hypothesized that dopaminergic circuitry would be more sensitive to stress in humans carrying the Ser23 variant. To test this hypothesis, we studied 54 healthy humans using positron emission tomography and the displaceable D(2)/D(3) receptor radiotracer [(11)C]raclopride. Binding potential (BP(ND)) was quantified before and after a standardized stress challenge consisting of 20 min of moderate deep muscular pain, and reduction in BP(ND) served as an index of dopamine release. The Cys23Ser variant was genotyped on a custom array, and ancestry informative markers were used to control for population stratification. We found greater dopamine release in the nucleus accumbens, caudate nucleus, and putamen among Ser23 carriers, after controlling for sex, age, and ancestry. Genotype accounted for 12% of the variance in dopamine release in the nucleus accumbens. There was no association of Cys23Ser with baseline BP(ND). These findings indicate that a putatively functional HTR2C variant (Ser23) is associated with greater striatal dopamine release during pain in healthy humans. Mesoaccumbal stress sensitivity may mediate the effects of HTR2C variation on risk of neuropsychiatric disorders.
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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.