Behavioral changes over time following ayahuasca exposure in zebrafish

Ayahuasca, a traditional Amazonian infusion made from Banisteriopsis caapi stem and Psychotria viridis leaves, contains N,N-dimethyltryptamine (DMT) and monoamine oxidase inhibitors. In adult zebrafish exposed to five concentrations (0, 0.1, 0.5, 1, and 3 ml/L, with 14 fish per group), swimming speed and distance traveled decreased with higher concentrations, while freezing and bottom dwelling increased at 1 and 3 ml/L. At 0.1 ml/L, bottom dwelling declined, suggesting reduced anxiety-like behavior. Low doses did not affect locomotion and appeared anxiolytic, whereas higher doses produced anxiogenic effects. Temporal behavioral analysis in zebrafish offers a sensitive method for studying ayahuasca-induced brain changes.

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Abstract

The combined infusion of Banisteriopsis caapi stem and Psychotria viridis leaves, known as ayahuasca, has been used for centuries by indigenous tribes. The infusion is rich in N, N-dimethyltryptamine (DMT) and monoamine oxidase inhibitors, with properties similar to those of serotonin. Despite substantial progress in the development of new drugs to treat anxiety and depression, current treatments have several limitations. Alternative drugs, such as ayahuasca, may shed light on these disorders. Here, we present time-course behavioral changes induced by ayahuasca in zebrafish, as first step toward establishing an ideal concentration for pre-clinical evaluations. We exposed adult zebrafish to five concentrations of the ayahuasca infusion: 0 (control), 0.1, 0.5, 1, and 3 ml/L (n D 14 each group), and behavior was recorded for 60 min. We evaluated swimming speed, distance traveled, freezing and bottom dwelling every min for 60 min. Swimming speed and distance traveled decreased with an increase in ayahuasca concentration while freezing increased with 1 and 3 ml/L. Bottom dwelling increased with 1 and 3 ml/L, but declined with 0.1 ml/L. Our data suggest that small amounts of ayahuasca do not affect locomotion and reduce anxiety-like behavior in zebrafish, while increased doses of the drug lead to crescent anxiogenic effects. We conclude that the temporal analysis of zebrafish behavior is a sensitive method for the study of ayahuasca-induced functional changes in the vertebrate brain