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Its psychoactive effects primarily stem from <jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>\u2010dimethyltryptamine (DMT). However, there is a lack of research on how and where AYA acts in the brain. This study addressed these questions by examining the extinction of aversive memories in AYA\u2010treated rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We focused on the 5\u2010HT<jats:sub>1A<\/jats:sub> and 5\u2010HT<jats:sub>2A<\/jats:sub> receptors, as DMT exhibits a high affinity for both of them, along with the infralimbic cortex in which activity and plasticity play crucial roles in regulating the mnemonic process under analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>A single oral treatment with AYA containing 0.3\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup> of DMT increased the within\u2010session extinction of contextual freezing behaviour without affecting its recall. This protocol, when repeated twice on consecutive days, enhanced extinction recall. These effects were consistent for both 1\u2010 and 21\u2010day\u2010old memories in males and females. AYA effects on fear extinction were independent of changes in anxiety and general exploratory activity: AYA\u2010 and vehicle\u2010treated animals showed no differences when tested in the elevated plus\u2010maze. The 5\u2010HT<jats:sub>2A<\/jats:sub> receptor antagonist MDL\u201011,939 and the 5\u2010HT<jats:sub>1A<\/jats:sub> receptor antagonist WAY\u2010100635 infused into the infralimbic cortex respectively blocked within\u2010 and between\u2010session fear extinction effects resulting from repeated oral administration of AYA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Our findings highlight complementary mechanisms by which AYA facilitates the behavioural suppression of aversive memories in the rat infralimbic cortex. These results suggest potential beneficial effects of AYA or DMT in stress\u2010related disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16315","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T08:08:24Z","timestamp":1707293304000},"page":"1671-1689","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Ayahuasca\u2010enhanced extinction of fear behaviour: Role of infralimbic cortex 5\u2010HT<sub>2A<\/sub> and 5\u2010HT<sub>1A<\/sub> receptors"],"prefix":"10.1111","volume":"181","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0870-1405","authenticated-orcid":false,"given":"Isabel","family":"Werle","sequence":"first","affiliation":[{"name":"Departamento de Farmacologia Universidade Federal de Santa Catarina  Florian\u00f3polis Santa Catarina Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8578-7273","authenticated-orcid":false,"given":"Laura M. 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