Abstract
Rationale
To uncover whether psychedelic drugs attenuate fear memory responses would advance the development of better psychedelic-based treatments for posttraumatic stress disorder (PTSD). Ayahuasca (AYA), a psychedelic brew containing indolamine N, N-dimethyltryptamine (DMT) and β-carbolines, facilitates fear extinction and improves neural plasticity. Upon retrieval, fear memory undergoes labilization and reconsolidation; however, the effects of AYA on this memory stabilization phase are unknown.
Objectives
We aimed to investigate the effects of AYA treatment on fear memory reconsolidation.
Methods
Fear-conditioned Wistar rats received AYA (60, 120, or 240 mg/kg) or H2O orally via gavage o.g. 20 min before, immediately, or 3 h after a short retrieval session. Analysis of AYA through liquid chromatography-tandem mass spectrometry was used to determine the content of DMT and β-carbolines in AYA.
Results
AYA impaired fear memory reconsolidation when given 20 min before or 3 h after memory retrieval, with the dose of 60 mg/kg being effective at both moments. This dose of AYA was devoid of anxiolytic effect. Importantly, during retrieval, AYA did not change fear expression. The lack of retrieval abolished the reconsolidation impairing effect of AYA. The effects of AYA treatment 20 min before or 3 h after memory retrieval lasted at least 22 days, suggesting no spontaneous recovery of fear memory. Fear memory impairments induced by AYA treatment, at both moments, do not show reinstatement.
Conclusions
Our findings support the view that a low dose of AYA treatment impairs early and late stages of memory reconsolidation instead of facilitating fear extinction.
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Acknowledgements
We thank Igreja União do Vegetal, Curitiba, PR, Brazil, for kindly donating the Ayahuasca.
Funding
This study was supported by Brazilian grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; 409255/2018–1). CAPES and CNPq had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
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D.M.D.: conducted the experiments; J.M.B.S.: conducted the EPM and neurochemical analysis; M.Y. and G.O.S.: conducted the ayahuasca analysis; D.M.D and C.A.J.S: data analysis and interpretation; D.M.D and C.A.J.S.: elaborated the work design, discussed the results; D.M.D, J.M.B.S., G.O.S, M.Y., and C.A.J.S.: wrote and revised the final manuscript.
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Daneluz, D.M., Sohn, J.M.B., Silveira, G.O. et al. Evidence on the impairing effects of Ayahuasca on fear memory reconsolidation. Psychopharmacology 239, 3325–3336 (2022). https://doi.org/10.1007/s00213-022-06217-2
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DOI: https://doi.org/10.1007/s00213-022-06217-2
