Avaliação dos efeitos alucinógenos e antidepressivos das fenetilaminas substituídas 25I-NBOME e 25I-NBOH em camundongos swiss

Abstract

New psychoactive substances (NPS) appear on the illegal market as alternatives to controlled or illicit drugs. Such is the diversity and complexity of NPS that many users may not be aware of the substances’ nature. The substituted phenethylamines 25INBOMe and 25I-NBOH are hallucinogenic NPS due to their agonistic effects on serotonin receptors. Several studies have shown the potential therapeutic use of hallucinogenic substances in mental conditions, including depression. However, there are no studies involving 25I-NBOMe and 25I-NBOH as possible antidepressants. In this sense, we evaluated their hallucinogenic and antidepressant effects in female Swiss mice on head twitch response (HTR) and immobility time, when evaluated in open field (OF) and forced swimming (FS) tests, respectively. For this, mice were treated with either 25INBOMe (0.3, 1 or 3 mg/Kg, i.p.), 25I-NBOH (0.3, 1 or 3 mg/Kg, i.p.), or vehicle (NaCl 0.9%+DMSO 0.3%), and immediately evaluated for 60 min in the OF. Alternatively, identically treated mice were subjected to FS after 40 min of treatment, when no changes in motor activity were observed. Our results show that both, 25I-NBOMe and 25I-NBOH, do not alter exploratory and anxiety-like behaviors in OF. However, they promote an increase in HTR in OF, indicating a hallucinogenic-like effect. In FS, only the lowest dose of 25I-NBOMe reduced immobility, indicating, for the first time, the antidepressantlike effect of the compound. These data increases evidence on the therapeutical potential of the use of hallucinogenic substances as antidepressants. Future studies are needed to further characterize 25I-NBOMe antidepressant-like effect, including alternative animal models and temporal evaluation.