NBOMe E NBOH: modulação psicodélica do comportamento tipo depressivo induzido por encefalopatia associada à sepse em roedores

Abstract

In the search for new therapeutic modalities, the medical and scientific community is betting on the therapeutic potential of psychedelic substances to establish a new era in the treatment of psychiatric disorders, especially mood disorders. Depression affects one in ten people worldwide and is characterized by episodes of depressed mood, loss of interest and pleasure. There are numerous modalities of antidepressant treatments available, however, less than 40% of patients respond to them, in addition, in the long term these drugs cause several side effects. Animal models are very convenient in the study of the pathophysiology of depression, however, some important aspects in the development of this disorder are still disregarded, such as neuroinflammation and synaptic plasticity. The objective of this study was to characterize an animal model for the study of depression through inflammation, based on surgical interventions of cecal ligation and perforation, and aimed at therapeutic intervention with synthetic psychedelic substances of the phenethylamine class, 25H-NBOMe and 25H-NBOH. For that, we used behavioral tests that predict depressive-like behavior in rodents, such as the forced swimming test and the open field test in the characterization of the experimental model, and also in the response to the administration of psychedelic substances. To assess the hallucinogenic potential of these substances, we proceeded with the Head-twitch response test, the HTR. In addition, biochemical tests were performed with brain structures collected from the animals belonging to this study, for the dosage of proteins and markers related to neuroinflammation, synaptic plasticity and depressive-like behavior: the glial acid fibrillar protein (GFAP), the density 95 postsynaptic protein (PSD-95), and synaptophysin. CLP surgery showed a satisfactory result in inducing depressive-like behavior in rodents, 7 and 14 days after performing the technique, and promoted an increase in GFAP in the prefrontal cortex of animals in the group that underwent experimental sepsis 14 days after this process; the psychedelic substance 25H-NBOMe demonstrated its antidepressant-like therapeutic potential against the modulation of anhedonic behaviors, such as immobility time in the forced swimming test, induced by our experimental model characterized for the study of depression and promoted increased expression of proteins which deficit is related to depression: synaptophysin and PDS-95 . These results suggest, for the first time, the antidepressant potential of psychedelics from the phenethylamine family and may contribute to advances in Experimental and Psychedelic Psychiatry.