Antidepressant-like effect of a selenopropargylic benzamide in mice: involvement of the serotonergic system
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ORIGINAL INVESTIGATION
Antidepressant-like effect of a selenopropargylic benzamide in mice: involvement of the serotonergic system Evelyn Mianes Besckow 1 & Natália Tavares Nonemacher 1 & Cleisson Schossler Garcia 1 & Carlos Natã da Silva Espíndola 1 & Éverton Berwanger Balbom 2 & Fabiane Gritzenco 2 & Lucielli Savegnago 3 & Benhur Godoi 2 & Cristiani Folharini Bortolatto 1 & César Augusto Brüning 1 Received: 15 October 2019 / Accepted: 26 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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 antidepressantlike 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. Keywords Major depressive disorder . Benzamide . Selenium . Serotonin . Tail suspension test
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00213-020-05600-1) contains supplementary material, which is available to authorized users. * Cristiani Folharini Bortolatto [email protected] * César Augusto Brüning [email protected] 1
Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Neurobiotechnology Research Group, Postgraduate Pr
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