ArticleThe European journal of neuroscience2009
Overexpression of 5-HT2C receptors in forebrain leads to elevated anxiety and hypoactivity.
Article in The European journal of neuroscience, 2009. 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.
What it found
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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, 44 citations in OpenAlex.
- Impact of GLP-1 Receptor Agonists on Suicide Behavior: A Meta-Analysis Based on Randomized Controlled Trials.Journal of diabetes · 2025 · on this mapPooled it
- Deconstruction of lysergic acid diethylamide.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Serotonin modulates social responses to stressed conspecifics via insular 5-HTNeuropharmacology · 2023Article
- Psychedelic-Induced Serotonin 2A Receptor Downregulation Does Not Predict Swim Stress Coping in Mice.International journal of molecular sciences · 2022Article
- Contribution of Corticotropin-Releasing Factor Receptor 1 (CRF1) to Serotonin Receptor 5-HTInternational journal of molecular sciences · 2019Article
- Alternative mRNA Splicing in the Pathogenesis of Obesity.International journal of molecular sciences · 2018Review
- 5-HTThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Input-specific contributions to valence processing in the amygdala.Learning & memory (Cold Spring Harbor, N.Y.) · 2016Review
- Amygdala-Hippocampal Phospholipase D (PLD) Signaling As Novel Mechanism of Cocaine-Environment Maladaptive Conditioned Responses.The international journal of neuropsychopharmacology · 2016Article
- Stress Modulation of Opposing Circuits in the Bed Nucleus of the Stria Terminalis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Review
- Ethanol induced adaptations in 5-HT2c receptor signaling in the bed nucleus of the stria terminalis: implications for anxiety during ethanol withdrawal.Neuropharmacology · 2015Article
- Genotype-Dependent Difference in 5-HT2C Receptor-Induced Hypolocomotion: Comparison with 5-HT2A Receptor Functional Activity.Neural plasticity · 2015Article
- Prevention of 5-hydroxytryptamine2C receptor RNA editing and alternate splicing in C57BL/6 mice activates the hypothalamic-pituitary-adrenal axis and alters mood.The European journal of neuroscience · 2014Article
- Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles.Therapeutic advances in psychopharmacology · 2014Review
- A novel aminotetralin-type serotonin (5-HT) 2C receptor-specific agonist and 5-HT2A competitive antagonist/5-HT2B inverse agonist with preclinical efficacy for psychoses.The Journal of pharmacology and experimental therapeutics · 2014Article
- RNA splicing and editing modulation of 5-HT(2C) receptor function: relevance to anxiety and aggression in VGV mice.Molecular psychiatry · 2013Article
- Differential distribution of serotonin receptor subtypes in BNST(ALG) neurons: modulation by unpredictable shock stress.Neuroscience · 2012Article
- A double dissociation in the effects of 5-HT2A and 5-HT2C receptors on the acquisition and expression of conditioned defeat in Syrian hamsters.Behavioral neuroscience · 2012Article
- Gene structure and expression of serotonin receptor HTR2C in hypothalamic samples from infanticidal and control sows.BMC neuroscience · 2012Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The 5-HT(2C) receptor has been implicated in mood and eating disorders. In general, it is accepted that 5-HT(2C) receptor agonists increase anxiety behaviours and induce hypophagia. However, pharmacological analysis of the roles of these receptors is hampered by the lack of selective ligands and the complex regulation of receptor isoforms and expression levels. Therefore, the exact role of 5-HT(2C) receptors in mood disorders remain controversial, some suggesting agonists and others suggesting antagonists may be efficacious antidepressants, while there is general agreement that antagonists are beneficial anxiolytics. In order to test the hypothesis that increased 5-HT(2C) receptor expression, and thus increased 5-HT(2C) receptor signalling, is causative in mood disorders, we have undertaken a transgenic approach, directly altering the 5-HT(2C) receptor number in the forebrain and evaluating the consequences on behaviour. Transgenic mice overexpressing 5-HT(2C) receptors under the control of the CaMKIIalpha promoter (C2CR mice) have elevated 5-HT(2C) receptor mRNA levels in cerebral cortex and limbic areas (including the hippocampus and amygdala), but normal levels in the hypothalamus, resulting in > 100% increase in the number of 5-HT(2C) ligand binding sites in the forebrain. The C2CR mice show increased anxiety-like behaviour in the elevated plus-maze, decreased wheel-running behaviour and reduced activity in a novel environment. These behaviours were observed in the C2CR mice without stimulation by exogenous ligands. Our findings support a role for 5-HT(2C) receptor signalling in anxiety disorders. The C2CR mouse model offers a novel and effective approach for studying disorders associated with 5-HT(2C) receptors.
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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.