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Ayahuasca-enhanced extinction of fear behaviour: Role of infralimbic cortex 5-HT2A and 5-HT1A receptors.

Isabel Werle, Laura M M Nascimento, Aymee L A Dos Santos, Luciane A Soares, Rafael G. Dos Santos, Jaime E. C. Hallak, Leandro J Bertoglio

British Journal of Pharmacology June 1, 2024 DOI: 10.1111/bph.16315 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Rats
Intervention Ayahuasca
Dose 0.3 mg·kg-1 of DMT
Duration Single treatment or two consecutive daily treatments
Topics Neuroplasticity PTSD Ayahuasca Serotonin
Keywords 5‐hydroxytryptamine Medial prefrontal cortex Psychedelics hallucinogens Entheogens Trauma Neuroscience brain research Psychoactive drugs Neurobiology Neural mechanisms Ayahuas
Citations 21
Key findings Ayahuasca facilitates extinction of aversive memories in rats through complementary 5-HT2A and 5-HT1A receptor mechanisms in the infralimbic cortex.

Abstract

Ayahuasca (AYA) is a botanical psychedelic with promising results in observational and small clinical trials for depression, trauma and drug use disorders. Its psychoactive effects primarily stem from N,N-dimethyltryptamine (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-treated rats. We focused on the 5-HT1A and 5-HT2A 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. A single oral treatment with AYA containing 0.3 mg·kg-1 of DMT increased the within-session 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- and 21-day-old memories in males and females. AYA effects on fear extinction were independent of changes in anxiety and general exploratory activity: AYA- and vehicle-treated animals showed no differences when tested in the elevated plus-maze. The 5-HT2A receptor antagonist MDL-11,939 and the 5-HT1A receptor antagonist WAY-100635 infused into the infralimbic cortex respectively blocked within- and between-session fear extinction effects resulting from repeated oral administration of AYA. 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-related disorders.

Comparable studies

Other preclinical and animal studies on ayahuasca, most cited first.

Study Year Design Participants
Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca Eight ayahuasca samples from Peru and several Banisteriopsis caapi cultivars 1984 Qualitative and quantitative chemical analysis with in vitro assay
The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains 2017 In vitro experimental study
N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice 2020 In vitro and in vivo experimental study
Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat Female Wistar rats 2015 Observational cohort
Effects of ayahuasca on the development of ethanol-induced behavioral sensitization and on a post-sensitization treatment in mice Mice 2015 Experimental study

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Neuroplasticity PTSD Ayahuasca Serotonin 5-MeO-DMT Anxiety DMT Depression