Evidence on the impairing effects of Ayahuasca on fear memory reconsolidation.

Abstract

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. We aimed to investigate the effects of AYA treatment on fear memory reconsolidation. Fear-conditioned Wistar rats received AYA (60, 120, or 240mg/kg) or H2O orally via gavage o.g. 20min before, immediately, or 3h 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. AYA impaired fear memory reconsolidation when given 20min before or 3h after memory retrieval, with the dose of 60mg/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 20min before or 3h aftermemory retrieval lasted at least 22days, suggesting no spontaneous recovery of fear memory. Fear memory impairments induced by AYA treatment, at both moments, do not show reinstatement. 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.