ArticleLearning & memory (Cold Spring Harbor, N.Y.)2014
Genetic variation in COMT activity impacts learning and dopamine release capacity in the striatum.
Article in Learning & memory (Cold Spring Harbor, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- The therapeutic potential of COMT inhibition: cognition and beyond.Molecular psychiatry · 2026Review
- An integrative multi-omics approach identifies microbiome alterations linked to pathological and behavioral features in autism spectrum disorder.Cell reports. Medicine · 2026Article
- Disentangling the Neural Circuits of Arousal and Anxiety-Like Behavior.Current topics in behavioral neurosciences · 2025Review
- Exploring Genetic and Receptor-Based Dopaminergic Strategies for Antidepressant Drug Development.Current gene therapy · 2025Review
- Motivational learning biases are differentially modulated by genetic determinants of striatal and prefrontal dopamine function.Journal of neural transmission (Vienna, Austria : 1996) · 2021Article
- The Associations between COMT and MAO-B Genetic Variants with Negative Symptoms in Patients with Schizophrenia.Current issues in molecular biology · 2021Article
- Gene-Environment Interactions in Developmental Neurotoxicity: a Case Study of Synergy between Chlorpyrifos and CHD8 Knockout in Human BrainSpheres.Environmental health perspectives · 2021Article
- Chronic Exposure to WIN55,212-2 During Adolescence Alters Prefrontal Dopamine Turnover and Induces Sensorimotor Deficits in Adult Rats.Neurotoxicity research · 2020Article
- Effort-related decision making in humanized COMT mice: Effects of ValPharmacology, biochemistry, and behavior · 2020Article
- Remote memories are enhanced by COMT activity through dysregulation of the endocannabinoid system in the prefrontal cortex.Molecular psychiatry · 2018Article
- Differential COMT expression and behavioral effects of COMT inhibition in male and female Wistar and alcohol preferring rats.Alcohol (Fayetteville, N.Y.) · 2018Article
- Haplotypic and Genotypic Association of Catechol-Frontiers in pharmacology · 2018Article
- Persistent gating deficit and increased sensitivity to NMDA receptor antagonism after puberty in a new mouse model of the human 22q11.2 microdeletion syndrome: a study in male mice.Journal of psychiatry & neuroscience : JPN · 2017Article
- COMT ValFrontiers in human neuroscience · 2017Article
- Contrasting Regulation of Catecholamine Neurotransmission in the Behaving Brain: Pharmacological Insights from an Electrochemical Perspective.Pharmacological reviews · 2017Review
- Genotype-Dependent Effects of COMT Inhibition on Cognitive Function in a Highly Specific, Novel Mouse Model of Altered COMT Activity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- COMT and ANKK1 Genetics Interact With Depression to Influence Behavior Following Severe TBI: An Initial Assessment.Neurorehabilitation and neural repair · 2016Article
- Association study of MiRSNPs with schizophrenia, tardive dyskinesia and cognition.Schizophrenia research · 2016Article
- Association between the dopamine D4 receptor gene exon III variable number of tandem repeats and political attitudes in female Han Chinese.Proceedings. Biological sciences · 2015Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
A common genetic polymorphism that results in increased activity of the dopamine regulating enzyme COMT (the COMT Val(158) allele) has been found to associate with poorer cognitive performance and increased susceptibility to develop psychiatric disorders. It is generally assumed that this increase in COMT activity influences cognitive function and psychiatric disease risk by increasing dopamine turnover in cortical synapses, though this cannot be directly measured in humans. Here we explore a novel transgenic mouse model of increased COMT activity, equivalent to the relative increase in activity observed with the human COMT Val(158) allele. By performing an extensive battery of behavioral tests, we found that COMT overexpressing mice (COMT-OE mice) exhibit cognitive deficits selectively in the domains that are affected by the COMT Val(158) allele, stimulus-response learning and working memory, functionally validating our model of increased COMT activity. Although we detected no changes in the level of markers for dopamine synthesis and dopamine transport, we found that COMT-OE mice display an increase in dopamine release capacity in the striatum. This result suggests that increased COMT activity may not only affect dopamine signaling by enhancing synaptic clearance in the cortex, but may also cause changes in presynaptic dopamine function in the striatum. These changes may underlie the behavioral deficits observed in the mice and might also play a role in the cognitive deficits and increased psychiatric disease risk associated with genetic variation in COMT activity in humans.
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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.