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Ayahuasca is a beverage obtained from the decoctions of Banisteriopsis caapi (Spruce ex Griseb.) Morton and Psychotria viridis Ruiz & Pav., used throughout the Amazon as a medicinal beverage for healing and spiritual exploration. The Banisteriopsis caapi extract consists of harmine, harmaline, and tetrahydroharmine (THH); which inhibit the isoforms of monoamine oxidase A and B. In the central nervous system (CNS), it can increase the norepinephrine (NE) concentration, produced in the Locus coeruleus (LC), reducing inflammation that is associated with some neurological disease, such as Parkinson's disease and Alzheimer's disease. evaluate the effects of treatment with B. caapi extract on the neuroinflammatory profile in animals with selective LC lesions. male Wistar rats with LC lesions induced by 6-hydroxydopamine were treated with B. caapi extract. Subsequently, behavioral tests were conducted, including the elevated plus maze, rotarod, and open field. Tyrosine hydroxylase positive (TH+) neurons and IBA-1 positive microglia were quantified from the LC inflammatory markers and free radical products were assessed. Both 6-Hydroxydopamine hydrochloride and the Banisteriopsis caapi extract causes reduction of LC neurons, at the concentration and frequency used. The LC depletion and the treatment of B. caapi extract interfere with locomotion. B. caapi extract and the LC lesion increased the number and activation of inflammatory cells, such as microglia. B. caapi extract decreases IL-10 in the hippocampus and BDNF gene expression. This study suggests that B. caapi extract (at the concentration and frequency used) promotes noradrenergic neuron depletion and creates a proinflammatory environment in the CNS. [Display omitted] • Treatment of Banisteriopsis caapi extract cause reduction of LC neurons. • LC depletion and the treatment of B. caapi extract interfere with locomotion. • B. caapi extract and the LC lesion increased the number and activation of inflammatory cells. • B. caapi extract decreases of BDNF genic expression in hippocampus. [ABSTRACT FROM AUTHOR]