Ayahuasca Pretreatment Prevents Sepsis-Induced Anxiety-Like Behavior, Neuroinflammation, and Oxidative Stress, and Increases Brain-Derived Neurotrophic Factor

The psychoactive decoction Ayahuasca (AYA) used for therapeutic and religious purposes by indigenous groups and peoples from Amazonian regions produces anti-inflammatory and neuroprotective effects. Thus, it may be useful to attenuate the neuroinflammation and related anxiety- and depressive-like symptoms elicited by inflammatory insults such as sepsis. Rats were pretreated for 3 days with different doses of AYA. Twenty-four hours after, cecal ligation and puncture (CLP) was performed. On days 1-4, post-CLP behavioral tests to assess anxiety-like behavior were performed. After 24-h, neuroinflammation, oxidative stress, myeloperoxidase activity, and mitochondrial metabolism were assessed in the prefrontal cortex (PFC), hippocampus (HP), and cortex. AYA pretreatment increased the time spent in the open arms of the elevated plus maze and prevented the sepsis-induced hyper-grooming and -rearing behavior, suggesting an anxiolytic effect. AYA pretreatment increased the levels of the anti-inflammatory interleukin 4, in the PFC and the cortex, and brain-derived neurotrophic factor in the cortex. Moreover, AYA pretreatment increased myeloperoxidase activity in the PFC and the HP and decreased nitrite/nitrate concentration in the PFC, HP, and cortex of septic rats, suggesting enhanced neutrophil activation and decreased nitric oxide signaling. Furthermore, AYA pretreatment prevented lipid peroxidation in the PFC, HP, and cortex of septic rats as measured by decreased levels of thiobarbituric acid reactive substances. Levels of protein carbonyls and activity of superoxide dismutase, citrate synthase, succinate dehydrogenase, and mitochondrial respiratory chain were not affected. Together, AYA represents a promising approach to prevent sepsis-induced neuroinflammatory and oxidative stress and associated anxiety-like symptoms.