ANTIDEPRESSANT-LIKE EFFECT OF 5-MEO-DMT AND NEUROCHEMICAL PROFILE IN MOUSE BRAIN

The psychedelic 5-MeO-DMT has gained attention in clinic for its ability to reduce depressive symptoms with fast onset of efficacy and short duration of psychedelic experience. Its mechanisms are still misunderstood. The data in animals reproduced its efficacy although most data are studied right after the stress procedure. Thus, postulating that 5-MeO-DMT could exert its therapeutic action via changes of pattern of neurochemicals across the brain, we first studied behavioral consequences of stress at distance from the stress procedure.
C57Bl6J male mice were used in this experiment. We performed a two-factors design where half of the cohort was submitted to stress of contention during three weeks. One week after the stress procedure, some stressed and non-stressed animals received 5-MeO-DMT (5mg/kg) or its solvent. The animals were evaluated in O-maze test, sucrose preference test, forced swim test (FST), tail suspension test (TST) during four days. Thereafter, animals were sacrificed to measure tissue monoamines and amino acids in 15 brain regions using High-Pressure Liquid Chromatography with Electrochemical Detection (HPLC-ECD) .
The stress procedure reduced sucrose consumption, and increased immobility time in the FST and TST, and the time in closed arms of the O-maze. 5-MeO-DMT, without effect by itself, suppressed the deficits in all tests except the O-maze paradigm. The neurochemical study is currently progressing.
The behavioral deficits, observable 7-10 days after the stress procedure, were ameliorated by 5-MeO-DMT except for the anxiety-like deficits. These results should reveal specific changes of connectivity of monoamines and amino acid transmitters in the brain.