Behavioral Changes Over Time Following Ayahuasca Exposure in Zebrafish

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.

Synergistic antidepressant- and anxiolytic-like effects of harmaline along with cinanserin in acute restraint stress-treated mice

“…***p < 0.001, **p < 0.01, and *p < 0.05 in comparison to saline/saline group. ++p < 0.01 and +p < 0.05 in compared with the saline/harmaline group neurotrophic factor (BDNF) (Abelaira et al 2013;Dos Santos et al 2016a, b;Moloudizargari et al 2013;Savoldi et al 2017;Splettstoesser et al 2005). So it can be concluded that harmaline induced antidepressant-and anxiolytic-like effects in the ARS mice by stimulation of neurogenesis, induction of neuroprotective properties, and inhibition of MAO-A as well as enhancement of serotonin concentrations in the brain (Biradar et al 2013;Dos Santos et al 2016a;Morales-Garcia et al 2017).…”

“…Harmaline commonly identified to provoke motor variations via activation of cells in the inferior olive (Hilber and Chapillon 2005 ). Besides, studies revealed that harmaline has antidepressive and anxiolytic properties that seem to be mediated by MAO inhibition and modulation of serotonin (5-HT), benzodiazepine, and dopamine receptors (Abelaira et al 2013 ; Dos Santos et al 2016a ; Dos Santos et al 2016b ; Savoldi et al 2017 ; Splettstoesser et al 2005 ). Interestingly, harmaline is endogenously produced in human and animal tissues as a low-molecular-weight product of secondary metabolism (Li et al 2017b , c ; Moloudizargari et al 2013 ).…”

Acute effects of ayahuasca in a juvenile non-human primate model of depression

“…The final batch was stored in glass bottles in a refrigerator. The main ayahuasca alkaloids were quantified at the beginning of the study using mass spectroscopy, resulting in values of 0.36±0.01 mg/mL DMT, 1.86±0.11 mg/mL harmine, 0.24±0.03 mg/mL harmaline, and 0.20±0.05 mg/mL THH 4,18. The tea used in this study was the same as that used in previous studies 4,18…”

Zebrafish as an Emerging Model System in the Global South: Two Decades of Research in Brazil

“…Finally, predictive validity shows how animal performance predicts the condition being tested. In Brazil, numerous neuroscience and behavioral studies have used the zebrafish as a model to understand the effects of coffee, 56,57 ayahuasca, 58,59 and alcohol. [60][61][62][63] This field is gaining importance worldwide, and new research partnerships are being established based on the know-how gained by Brazilian researchers.…”