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 = 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.
Highlights
The ayahuasca brew has been used for centuries for religious and medicinal purposes by a number of groups in South America, notably the indigenous people from the Amazon region (McKenna et al, 1984)
In addition to the protective effect of DMT, the inhibition of MAO itself modulates the viability of monoaminergic neurotransmitters, increasing its bioavailability (McKenna et al, 1984; Riba et al, 2003)
We observed that ayahuasca affects both locomotor and anxiety-like behaviors in zebrafish (Danio rerio)
Summary
The ayahuasca brew has been used for centuries for religious and medicinal purposes by a number of groups in South America, notably the indigenous people from the Amazon region (McKenna et al, 1984). Ayahuasca is traditionally made from the decoction of Banisteriopsis caapi stalks and Psychotria viridis leaves. Banisteriopsis caapi contains the alkaloids harmine, tetrahydroharmine (THH) and, in smaller amounts, harmaline, all belonging to the β-carboline group, in addition to monoamine oxidase inhibitors (MAOIs). P. viridis is rich in N, N-dimethyltryptamine (DMT) (McKenna et al, 1984; Riba et al, 2003). In addition to the protective effect of DMT, the inhibition of MAO itself modulates the viability of monoaminergic neurotransmitters (serotonin, noradrenaline, and dopamine), increasing its bioavailability (McKenna et al, 1984; Riba et al, 2003). DMT’s properties are similar to those of serotonin and other tryptamines, such as psilocybin, and act essentially as agonists on 5-HT2A and 5HT2C receptors (Ray, 2010)
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