Abstract
Rationale
Major depressive disorder is a psychiatric disorder that requires considerable attention, since it dramatically impairs the quality of life of the sufferers. The available treatments do not have the efficacy needed, often presenting several side effects. Organoselenium compounds and benzamides have presented some pharmacological properties, among them an antidepressant-like effect.
Objectives and methods
This study evaluated the antidepressant-like effect of N-(3-(phenylselanyl)prop-2-yn-1-yl)benzamide (SePB), an organoselenium compound containing a benzamide moiety, on the forced swimming test (FST) and the tail suspension test (TST) in mice, as well as the involvement of the serotonergic system in its effect.
Results
SePB, tested after different times (15–120 min) and doses (1–50 mg/kg, intragastrically (i.g.)), reduced immobility of male mice during FST and TST, without changing locomotor activity in the open-field test (OFT), demonstrating its antidepressant-like effect. SePB (10 mg/kg) also produced an antidepressant-like effect in female mice in the TST. The preadministration of the serotonin (5-HT) depletor p-chlorophenylalanine (pCPA; 100 mg/kg, intraperitoneal route (i.p.) once daily for 4 days) prevented the anti-immobility effect of SePB, indicating that the serotonergic system is involved in the SePB antidepressant-like effect. The preadministration of the selective serotonergic receptor antagonists WAY100635 (0.1 mg/kg, subcutaneous route (s.c.), a selective 5-HT1A receptor antagonist), ketanserin (1 mg/kg, i.p., a 5-HT2A/2C receptor antagonist), and ondansetron (1 mg/kg, i.p., a selective 5-HT3 receptor antagonist) also prevented the anti-immobility effect of SePB, demonstrating that these receptors are involved in the antidepressant-like effect of SePB.
Conclusion
The search for new antidepressants drugs is a noteworthy goal. This study has described a new compound with an antidepressant-like effect, whose mechanism of action is related to modulation of the serotonergic system.
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Funding
We gratefully recognize Universidade Federal de Pelotas (UFPel), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/PROAP), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, grant numbers 420386/2018-1 and 438384/2018-0) for the financial support. C.S.G. is a recipient of the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) fellowship.
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The experiments were conducted according to the standards of the UFPel Animal Ethics and Welfare Committee (CEEA 4903-2017), affiliated to the Council for Control of Animal Experiments (CONCEA), and according to the National Institutes of Health Guide for the care and use of laboratory animals (NIH Publications No. 8023, revised 1978). Every effort has been made to minimize animal suffering and reduce the number of animals used in the experiments.
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Besckow, E.M., Nonemacher, N.T., Garcia, C.S. et al. Antidepressant-like effect of a selenopropargylic benzamide in mice: involvement of the serotonergic system. Psychopharmacology 237, 3149–3159 (2020). https://doi.org/10.1007/s00213-020-05600-1
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DOI: https://doi.org/10.1007/s00213-020-05600-1