ArticleMolecular psychiatry2021
Distinct roles for dopamine clearance mechanisms in regulating behavioral flexibility.
Article in Molecular psychiatry, 2021. 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, 30 citations in OpenAlex.
- Catechol-O-methyltransferase activity does not influence emotional processing in men.Journal of psychopharmacology (Oxford, England) · 2022Trial
- The therapeutic potential of COMT inhibition: cognition and beyond.Molecular psychiatry · 2026Review
- Depression in neurodegenerative disease: neurobiological mechanisms and emerging treatments.Molecular psychiatry · 2026Review
- Effects of Lacticaseibacillus rhamnosus L156.4 and Lactococcus lactis NCDO 2118 strains on reducing alcohol intake and preference in an animal model of high alcohol consumption and preference.Scientific reports · 2026Article
- Synaptogyrin-3 plays a critical role in addiction-related dopamine dysfunction and behavioral maladaptations.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Biogenic Amine Metabolism and Its Genetic Variations in Autism Spectrum Disorder: A Comprehensive Overview.Biomolecules · 2025Review
- Frontostriatal circuit dysfunction leads to cognitive inflexibility in neuroligin-3 R451C knockin mice.Molecular psychiatry · 2024Article
- A biophysical model for dopamine modulating working memory through reward system in obsessive-compulsive disorder.Cognitive neurodynamics · 2024Article
- Dopamine-independent effect of rewards on choices through hidden-state inference.Nature neuroscience · 2024Article
- Dissociable effects of dopaminergic medications on depression symptom dimensions in Parkinson disease.Nature. Mental health · 2024Article
- Gut microbiota metabolites: potential therapeutic targets for Alzheimer's disease?Frontiers in pharmacology · 2024Review
- Dissociable effects of dopaminergic medications on depression symptom dimensions in Parkinson's disease.medRxiv : the preprint server for health sciences · 2023Article
- Cortico-striatal networking deficits associated with advanced HIV disease and cocaine use.Journal of neurovirology · 2023Article
- Adolescent sleep molds adult social preferences.Nature neuroscience · 2022Article
- Phasic Dopamine Changes and Hebbian Mechanisms during Probabilistic Reversal Learning in Striatal Circuits: A Computational Study.International journal of molecular sciences · 2022Article
- Dopaminergic challenge dissociates learning from primary versus secondary sources of information.eLife · 2022Article
- Open-source, Python-based, hardware and software for controlling behavioural neuroscience experiments.eLife · 2022Article
- Social Determinants of Inter-Individual Variability and Vulnerability: The Role of Dopamine.Frontiers in behavioral neuroscience · 2022Review
- Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Dopamine plays a crucial role in adaptive behavior, and dysfunctional dopamine is implicated in multiple psychiatric conditions characterized by inflexible or inconsistent choices. However, the precise relationship between dopamine and flexible decision making remains unclear. One reason is that, while many studies have focused on the activity of dopamine neurons, efficient dopamine signaling also relies on clearance mechanisms, notably the dopamine transporter (DAT), which predominates in striatum, and catechol-O-methyltransferase (COMT), which predominates in cortex. The exact locus, extent, and timescale of the effects of DAT and COMT are uncertain. Moreover, there is limited data on how acute disruption of either mechanism affects flexible decision making strategies mediated by cortico-striatal networks. To address these issues, we combined pharmacological modulation of DAT and COMT with electrochemistry and behavior in mice. DAT blockade, but not COMT inhibition, regulated sub-second dopamine release in the nucleus accumbens core, but surprisingly neither clearance mechanism affected evoked release in prelimbic cortex. This was not due to a lack of sensitivity, as both amphetamine and atomoxetine changed the kinetics of sub-second release. In a multi-step decision making task where mice had to respond to reversals in either reward probabilities or the choice sequence to reach the goal, DAT blockade selectively impaired, and COMT inhibition improved, performance after reward reversals, but neither manipulation affected the adaptation of choices after action-state transition reversals. Together, our data suggest that DAT and COMT shape specific aspects of behavioral flexibility by regulating different aspects of the kinetics of striatal and cortical dopamine, respectively.
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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.