ArticleeLife2021
L-DOPA modulates activity in the vmPFC, nucleus accumbens, and VTA during threat extinction learning in humans.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Examining the relationship between pre-treatment anhedonia and treatment outcomes in individuals with anxiety or depression: A systematic review.Journal of affective disorders · 2026Pooled it
- Effects of Dopaminergic Therapy with Levodopa (L-DOPA) on Fear and Anxiety-Related Circuits and Symptoms in Patients with Depression and Higher Inflammation.Brain, behavior, and immunity · 2026Trial
- Nicotine reduces discrimination between threat and safety in the hippocampus, nucleus accumbens and amygdala.Translational psychiatry · 2024Trial
- Dopamine D2/3 receptors and functional connectivity during fear extinction: A PET-fMRI study.Neuroimage. Reports · 2026Article
- Age and loneliness relate to reduced trust learning and alterations in amygdala function.iScience · 2026Article
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- Event Segmentation Promotes the Reorganization of Emotional Memory.Journal of cognitive neuroscience · 2025Article
- Current State of the Neuroscience of Fear Extinction and Its Relevance to Anxiety Disorders.Current topics in behavioral neurosciences · 2025Review
- Fear extinction rescuing effects of dopamine and L-DOPA in the ventromedial prefrontal cortex.Translational psychiatry · 2024Article
- Prefrontal Dopamine in Flexible Adaptation to Environmental Changes: A Game for Two Players.Biomedicines · 2023Review
- Closed-loop brain stimulation augments fear extinction in male rats.Nature communications · 2023Article
- Alleviating anxiety and taming trauma: Novel pharmacotherapeutics for anxiety disorders and posttraumatic stress disorder.Neuropharmacology · 2023Review
- Mechanisms through which exercise reduces symptom severity and/or functional impairment in posttraumatic stress disorder (PTSD): Protocol for a living systematic review of human and non-human studies.Wellcome open research · 2023Article
- Acquisition of threat responses are associated with elevated plasma concentration of endocannabinoids in male humans.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Cortico-Striatal Activity Characterizes Human Safety Learning via Pavlovian Conditioned Inhibition.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Anhedonia in Anxiety Disorders.Current topics in behavioral neurosciences · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Learning to be safe is central for adaptive behaviour when threats are no longer present. Detecting the absence of an expected threat is key for threat extinction learning and an essential process for the behavioural treatment of anxiety-related disorders. One possible mechanism underlying extinction learning is a dopaminergic mismatch signal that encodes the absence of an expected threat. Here we show that such a dopamine-related pathway underlies extinction learning in humans. Dopaminergic enhancement via administration of L-DOPA (vs. Placebo) was associated with reduced retention of differential psychophysiological threat responses at later test, which was mediated by activity in the ventromedial prefrontal cortex that was specific to extinction learning. L-DOPA administration enhanced signals at the time-point of an expected, but omitted threat in extinction learning within the nucleus accumbens, which were functionally coupled with the ventral tegmental area and the amygdala. Computational modelling of threat expectancies further revealed prediction error encoding in nucleus accumbens that was reduced when L-DOPA was administered. Our results thereby provide evidence that extinction learning is influenced by L-DOPA and provide a mechanistic perspective to augment extinction learning by dopaminergic enhancement in humans.
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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.