ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
Stimulation of 5-HT2C receptors improves cognitive deficits induced by human tryptophan hydroxylase 2 loss of function mutation.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Serotonergic System Dysregulation in Alzheimer's Disease.ACS chemical neuroscience · 2026Review
- The Complex Role of Serotonin-Dopamine-Glutamate Receptors in Major Depression.Advances in experimental medicine and biology · 2026Review
- Tryptophan hydroxylase 2 deficiency alters autism-related behavioural phenotypes in rats.Scientific reports · 2025Article
- Serotonin dysfunction in ADHD.Journal of neurodevelopmental disorders · 2025Review
- Fetal cannabidiol (CBD) exposure alters thermal pain sensitivity, problem-solving, and prefrontal cortex excitability.Molecular psychiatry · 2023Article
- Adverse maternal environment affects hippocampal HTR2c variant expression and epigenetic characteristics in mouse offspring.Pediatric research · 2022Article
- Autism-like behaviors regulated by the serotonin receptor 5-HT2B in the dorsal fan-shaped body neurons of Drosophila melanogaster.European journal of medical research · 2022Article
- Impact of specific serotonin receptor modulation on behavioral flexibility.Pharmacology, biochemistry, and behavior · 2021Review
- Chronic Lorcaserin Treatment Reverses the Nicotine Withdrawal-Induced Disruptions to Behavior and Maturation in Developing Neurons in the Hippocampus of Rats.International journal of molecular sciences · 2021Article
- Biological Timing and Neurodevelopmental Disorders: A Role for Circadian Dysfunction in Autism Spectrum Disorders.Frontiers in neuroscience · 2021Review
- Alteration of Gut Microbiota in Autism Spectrum Disorder: An Overview.Soa--ch'ongsonyon chongsin uihak = Journal of child & adolescent psychiatry · 2020Review
- Development of the Korean Form of the Premonitory Urge for Tics Scale: A Reliability and Validity Study.Soa--ch'ongsonyon chongsin uihak = Journal of child & adolescent psychiatry · 2020Article
- Risperidone stimulates food intake and induces body weight gain via the hypothalamic arcuate nucleus 5-HT2c receptor-NPY pathway.CNS neuroscience & therapeutics · 2020Article
- New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties.Journal of experimental pharmacology · 2020Article
- Effects of long-term high-fat food or methamphetamine intake and serotonin 2C receptors on reversal learning in female rhesus macaques.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- Perinatal SSRI exposure permanently alters cerebral serotonin receptor mRNA in mice but does not impact adult behaviors.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2018Article
- The serotonin system in autism spectrum disorder: From biomarker to animal models.Neuroscience · 2016Review
- Further Advances in Optimizing (2-Phenylcyclopropyl)methylamines as Novel Serotonin 2C Agonists: Effects on Hyperlocomotion, Prepulse Inhibition, and Cognition Models.Journal of medicinal chemistry · 2016Article
- The serotonergic system and cognitive function.Translational neuroscience · 2016Review
- Translational Mouse Models of Autism: Advancing Toward Pharmacological Therapeutics.Current topics in behavioral neurosciences · 2016Review
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
Polymorphisms in the gene encoding the serotonin synthesis enzyme Tph2 have been identified in mental illnesses, including bipolar disorder, major depression, autism, schizophrenia, and ADHD. Deficits in cognitive flexibility and perseverative behaviors are shared common symptoms in these disorders. However, little is known about the impact of Tph2 gene variants on cognition. Mice expressing a human TPH2 variant (Tph2-KI) were used to investigate cognitive consequences of TPH2 loss of function and pharmacological treatments. We applied a recently developed behavioral assay, the automated H-maze, to study cognitive functions in Tph2-KI mice. This assay involves the consecutive discovery of three different rules: a delayed alternation task, a non-alternation task, and a delayed reversal task. Possible contribution of locomotion, reward, and sensory perception were also investigated. The expression of loss-of-function mutant Tph2 in mice was associated with impairments in reversal learning and cognitive flexibility, accompanied by perseverative behaviors similar to those observed in human clinical studies. Pharmacological restoration of 5-HT synthesis with 5-hydroxytryptophan or treatment with the 5-HT(2C) receptor agonist CP809.101 reduced cognitive deficits in Tph2-KI mice and abolished perseveration. In contrast, treatment with the psychostimulant methylphenidate exacerbated cognitive deficits in mutant mice. Results from this study suggest a contribution of TPH2 in the regulation of cognition. Furthermore, identification of a role for a 5-HT(2) receptor agonist as a cognition-enhancing agent in mutant mice suggests a potential avenue to explore for the personalized treatment of cognitive symptoms in humans with reduced 5-HT synthesis and TPH2 polymorphisms.
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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.