Ayahuasca prevents oxidative stress in a rat model of depression elicited by unpredictable chronic mild stress

Ayahuasca, a traditional entheogenic beverage, was tested as a potential antidepressant in rats exposed to unpredictable chronic mild stress. Daily administration of 500 mg/kg for 15 days did not prevent anhedonia-like behavior, a core symptom of depression. However, ayahuasca counteracted stress-induced increases in TBARS and nitrite levels in the cerebral cortex and restored decreased catalase and hippocampal sulfhydryl levels, suggesting an adaptogenic antioxidant molecular mechanism. Locomotion was unaffected. The findings indicate that ayahuasca may mitigate some biochemical changes associated with stress-induced depression without altering behavior in non-stressed rats.

Study at a glance

Abstract

ABSTRACT Background: Depression is a highly disabling common mental disorder and, due to its multifactorial nature, the development of effective therapies is challenging and of great relevance. Ayahuasca (AYA), an entheogenic traditional beverage, has emerged as an alternative for antidepressant treatment, however, AYA preclinical and clinical trials are still incipient. Objectives: This investigation aimed to evaluate some behavioral and biochemical effects of AYA subchronic administration in rats submitted to a model of depression elicited by unpredictable chronic mild stress (UCMS). Methods: 500 mg/kg of AYA was administered in adult male rats once a day for 15 days before submitting the animals to UCMS. Anhedonia-like and locomotion behavior, lipid peroxidation, antioxidant enzyme activities, and sulfhydryl/nitrite content were evaluated. Results: AYA intake failed to prevent anhedonia-like behavior. Locomotion was not altered by AYA consumption or by the experimental condition. UCMS increased TBARS and nitrites levels, decreased the levels of catalase in the cerebral cortex and of Sulfhydryl in the hippocampus. AYA treatment counteracted these biochemical alterations but did not display any alterations in non-stressed rats. Conclusions: Taken together, results indicate an adaptogenic antioxidant molecular mechanism of AYA in relation to depression induced by stress.