ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2022
Effects of a psychedelic 5-HT2A receptor agonist on anxiety-related behavior and fear processing in mice.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Resetting the hippocampal buffer: a neurocognitive account of psychedelic therapy for anxiety-related psychopathology.Psychopharmacology · 2026Review
- Psychedelic 4-AcO-DMT attenuated looming-induced freezing behaviors by activating PrLMolecular psychiatry · 2026Article
- Mild concussion impairs extinction of avoidance and alters respective brain circuits in male rats.Experimental neurology · 2026Article
- Learning as the unifying mechanism of psychedelic action.Journal of psychopharmacology (Oxford, England) · 2026Review
- The psychoplastogen tabernanthalog induces neuroplasticity without proximate immediate early gene activation.Nature neuroscience · 2025Article
- Biased signalingActa pharmaceutica Sinica. B · 2025Review
- Evaluation of behavioural and neurochemical effects of psilocybin in mice subjected to chronic unpredictable mild stress.Translational psychiatry · 2025Article
- Exploring the therapeutic potential of psychedelics: Fear extinction mechanisms and amygdala modulation.Psychedelics · 2025Article
- Ventral hippocampal parvalbumin interneurons gate the acute anxiolytic action of the serotonergic psychedelic DOI.Neuron · 2024Article
- Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states.Science (New York, N.Y.) · 2024Article
- Desloratadine ameliorates paclitaxel-induced peripheral neuropathy and hypersensitivity reactions in mice.Acta pharmacologica Sinica · 2024Article
- Psilocybin Facilitates Fear Extinction: Importance of Dose, Context, and Serotonin Receptors.ACS chemical neuroscience · 2024Article
- Ethnomedicinal Study and Evaluation of the Anxiolytic-like and Diuretic Effects of the OrchidPharmaceuticals (Basel, Switzerland) · 2024Article
- Ethopharmacological evaluation of antidepressant-like effect of serotonergic psychedelics in C57BL/6J male mice.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Psilocybin analog 4-OH-DiPT enhances fear extinction and GABAergic inhibition of principal neurons in the basolateral amygdala.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Antidepressant-like effects of psychedelics in a chronic despair mouse model: is the 5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Accelerated TMS - moving quickly into the future of depression treatment.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Article
- Sex-specific effects of psychedelic drug exposure on central amygdala reactivity and behavioral responding.Translational psychiatry · 2023Article
- Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment.Neuropharmacology · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Psychedelic-assisted psychotherapy gained considerable interest as a novel treatment strategy for fear-related mental disorders but the underlying mechanism remains poorly understood. The serotonin 2A (5-HT2A) receptor is a key target underlying the effects of psychedelics on emotional arousal but its role in fear processing remains controversial. Using the psychedelic 5-HT2A/5-HT2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) and 5-HT2A receptor knockout (KO) mice we investigated the effect of 5-HT2A receptor activation on emotional processing. We show that DOI administration did not impair performance in a spontaneous alternation task but reduced anxiety-like avoidance behavior in the elevated plus maze and elevated zero maze tasks. Moreover, we found that DOI did not block memory recall but diminished fear expression in a passive avoidance task. Likewise, DOI administration reduced fear expression in an auditory fear conditioning paradigm, while it did not affect retention of fear extinction when administered prior to extinction learning. The effect of DOI on fear expression was abolished in 5-HT2A receptor KO mice. Administration of DOI induced a significant increase of c-Fos expression in specific amygdalar nuclei. Moreover, local infusion of the 5-HT2A receptor antagonist M100907 into the amygdala reversed the effect of systemic administration of DOI on fear expression while local administration of DOI into the amygdala was sufficient to suppress fear expression. Our data demonstrate that activation of 5-HT2A receptors in the amygdala suppresses fear expression but provide no evidence for an effect on retention of fear extinction.
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