ArticleTranslational psychiatry2016
Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction.
Article in Translational psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 69 citations in OpenAlex.
- L-DOPA improves extinction memory retrieval after successful fear extinction.Psychopharmacology · 2019Trial
- Fear expression is suppressed by tyrosine administration.Scientific reports · 2019Trial
- Effects of novelty and reward-based fear extinction on memory generalization.Behaviour research and therapy · 2026Article
- When Safety Fails to Update: Altered Dopamine Prediction Signals in Extinction-Deficient Mice.eNeuro · 2026Article
- Article
- Effects of TrkB-related induced metaplasticity within the BLA on anxiety, extinction learning, and plasticity in BLA-modulated brain regions.Behavioral and brain functions : BBF · 2025Article
- Current State of the Neuroscience of Fear Extinction and Its Relevance to Anxiety Disorders.Current topics in behavioral neurosciences · 2025Review
- Substance withdrawal during psychotherapy incorporating equines: A preliminary investigation of the role of neurotransmitters during treatment.Journal of equine rehabilitation · 2025Article
- Interrelated involvement of the endocannabinoid/endovanilloid (TRPV1) systems and epigenetic processes in anxiety- and working memory impairment-related behavioural effects of nicotine as a stressor.Addiction biology · 2024Article
- Replication study on the role of dopamine-dependent prefrontal reactivations in human extinction memory retrieval.Nature communications · 2024Article
- Fear extinction rescuing effects of dopamine and L-DOPA in the ventromedial prefrontal cortex.Translational psychiatry · 2024Article
- Monoamine Oxidase: A Potential Link in Papez Circuit to Generalized Anxiety Disorders.CNS & neurological disorders drug targets · 2024Review
- Epigenetics of Fear, Anxiety and Stress - Focus on Histone Modifications.Current neuropharmacology · 2024Article
- The role of epigenetics in anxiety disorders.Molecular biology reports · 2023Review
- By what molecular mechanisms do social determinants impact cardiometabolic risk?Clinical science (London, England : 1979) · 2023Review
- Alleviating anxiety and taming trauma: Novel pharmacotherapeutics for anxiety disorders and posttraumatic stress disorder.Neuropharmacology · 2023Review
- Role of Microbiota-Gut-Brain Axis in Regulating Dopaminergic Signaling.Biomedicines · 2022Review
- Mitochondrial brain proteome acetylation levels and behavioural responsiveness to amphetamine are altered in mice lacking Sirt3.Frontiers in physiology · 2022Article
- Altered sleep behavior in a genetic mouse model of impaired fear extinction.Scientific reports · 2021Article
- Dopamine in Fear Extinction.Frontiers in synaptic neuroscience · 2021Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a potential gene-regulatory mechanism. Although enhancing histone acetylation, via administering the histone deacetylase (HDAC) inhibitor MS-275, does not induce fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated as shown following a mild conditioning protocol. This was associated with enhanced histone acetylation in neurons of the mPFC and amygdala. Finally, as a proof-of-principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. In summary, current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear-inhibitory memory.
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