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Effects of repeated ayahuasca administration on behaviour and c-Fos expression in male rats exposed to the open field

Dimitri Daldegan-Bueno, Vanessa Manchim Favaro, Paulo Rogério Morais, Alessandra Sussulini, Maria Gabriela Menezes Oliveira

Behavioural Brain Research April 1, 2022 DOI: 10.1016/j.bbr.2022.113878 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Animal experimental study Peer reviewed
Population Male Wistar rats
Intervention Ayahuasca
Dose 120, 240, 480 or 3600 mg/kg
Duration 30-day administration, assessed one hour after last dose
Topics Anxiety Ayahuasca Serotonin
Keywords Anxiogenic Open field Basolateral amygdala Hippocampus Elevated plus maze Anxiolytic C-fos Cortex anatomy Pharmacology
Citations 10
Key findings Repeated ayahuasca administration produced a stimulant-like effect at low doses and decreased activity at very high doses, with no evidence of an anxiolytic effect in a novel anxiogenic environment.

Abstract

Considering the long-lasting effects of ayahuasca on the brain and emotional processing, the objective of this study was to evaluate the behavioural and neurobiological effects of repeated ayahuasca administration in an animal model of exploratory behaviour related to novel-environment anxiety. Male Wistar rats received water, 120, 240, 480 or 3600 mg/kg of resuspended freeze-dried ayahuasca by gavage once a day for 30 days; there was also a non-manipulated homecage group. One hour after the last administration, animals were placed individually in the open field for 20 min. We analysed the weight gain, the behavioural response through a stochastic analysis, and c-Fos immunoreactive levels in the hippocampus, amygdala, pre-frontal and barrel field cortex. Ayahuasca at 120 mg/kg increased ambulation, and at 3600 mg/kg decreased vertical exploration and reduced weight gain. Aya3600 had higher c-Fos expression in regions of the hippocampus and infralimbic cortex than homecage, water or aya120 groups. Water-receiving animals had less c-Fos expression in the anterior basolateral amygdala than others groups. Our results show different behavioural effects of ayahuasca: a stimulant-like effect in small doses, and decreased activity in extreme high-dose, probably due to adverse effects. Higher activation of areas involved in emotional processing and the serotonergic pathway adds to the neurobiological literature on repeated/chronic ingestion of ayahuasca. Our data do not support an anxiolytic effect of repeated ayahuasca related to exploring new anxiogenic-environment but suggest that low ayahuasca doses should be further studied. The absence of severe impairment and behavioural syntax alteration reinforce ayahuasca safety.

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