ArticleThe international journal of neuropsychopharmacology2021
A Complex Impact of Systemically Administered 5-HT2A Receptor Ligands on Conditioned Fear.
Article in The international journal of neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- The effect of SSRIs on unconditioned anxiety: a systematic review and meta-analysis of animal studies.Psychopharmacology · 2024Pooled it
- Adjunctive Pharmacotherapy for Major Depressive Disorder with Anxiety Symptoms: from Monoamines to Recent Clinical Evidence.CNS drugs · 2026Review
- Acute psilocybin or ethocybin leads to a sustained increase in Pavlovian aversion memory in male mice.Frontiers in pharmacology · 2026Article
- (-)-OSU6162 reduces freezing elicited by context-conditioned fear in rats.Journal of psychopharmacology (Oxford, England) · 2025Article
- Psilocybin Enhances Cued Fear Extinction and Extinction Recall in Stress-Naïve, Acutely Stressed, and Chronically Stressed Mice.ACS pharmacology & translational science · 2025Article
- Advanced pharmacological and pharmacokinetic evaluation of 1,3 dimethylpurine-2,6-dione derivative (GR-14) with prominent mood-modulating activity in rats.Pharmacological reports : PR · 2025Article
- Exploring the therapeutic potential of psychedelics: Fear extinction mechanisms and amygdala modulation.Psychedelics · 2025Article
- Review
- Effects of psilocybin on uncertain punishment learning.Neurobiology of learning and memory · 2024Article
- Psilocybin Facilitates Fear Extinction: Importance of Dose, Context, and Serotonin Receptors.ACS chemical neuroscience · 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
- Molecular and Medical Aspects of Psychedelics.International journal of molecular sciences · 2023Review
- Psychedelics for military and Veteran communities? Research, practice, and policy considerations.Journal of military, veteran and family health · 2023Article
- Median raphe serotonergic neurons projecting to the interpeduncular nucleus control preference and aversion.Nature communications · 2022Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThough drugs binding to serotonergic 5-HT2A receptors have long been claimed to influence human anxiety, it remains unclear if this receptor subtype is best described as anxiety promoting or anxiety dampening. Whereas conditioned fear expressed as freezing in rats is modified by application of 5-HT2A-acting drugs locally into different brain regions, reports on the effect of systemic administration of 5-HT2A receptor agonists and 5-HT2A antagonists or inverse agonists on this behavior remain sparse.
methodsWe assessed the possible impact of systemic administration of 5-HT2A receptor agonists, 5-HT2A receptor inverse agonists, and a selective serotonin reuptake inhibitor (SSRI)-per se or in combination-on the freezing displayed by male rats when re-exposed to a conditioning chamber in which they received foot shocks 7 days earlier.
resultsThe 5-HT2A receptor agonists psilocybin and 25CN-NBOH induced a reduction in conditioned fear that was countered by pretreatment with 5-HT2A receptor inverse agonist MDL 100907. While both MDL 100907 and another 5-HT2A receptor inverse agonist, pimavanserin, failed to impact freezing per se, both compounds unmasked a robust fear-reducing effect of an SSRI, escitalopram, which by itself exerted no such effect.
conclusionsThe results indicate that 5-HT2A receptor activation is not a prerequisite for normal conditioned freezing in rats but that this receptor subtype, when selectively over-activated prior to expression, exerts a marked fear-reducing influence. However, in the presence of an SSRI, the 5-HT2A receptor, on the contrary, appears to counter an anti-freezing effect of the enhanced extracellular serotonin levels following reuptake inhibition.
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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.