Effects of a psychedelic 5-HT2A receptor agonist on anxiety-related behavior and fear processing in mice

Autor: Błażej D. Pędzich, Sarah Rubens, Mehdi Sekssaoui, Anouk Pierre, Andries Van Schuerbeek, Philippe Marin, Joel Bockaert, Emmanuel Valjent, Carine Bécamel, Dimitri De Bundel
Přispěvatelé: Faculty of Medicine and Pharmacy, Pharmaceutical and Pharmacological Sciences, Experimental Pharmacology, Guerineau, Nathalie C., Vrije Universiteit Brussel (VUB), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Neuropsychopharmacology
Neuropsychopharmacology, 2022, 47 (7), pp.1304-1314. ⟨10.1038/s41386-022-01324-2⟩
ISSN: 0893-133X
0007-0920
Popis: International audience; 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.
Databáze: OpenAIRE
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