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Psychopharmacology (Berl) ; 237(10): 3149-3159, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32617647

RESUMO

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.


Assuntos
Antidepressivos/uso terapêutico , Benzamidas/uso terapêutico , Compostos Organosselênicos/uso terapêutico , Antagonistas da Serotonina/farmacologia , Serotonina/metabolismo , Animais , Antidepressivos/química , Benzamidas/química , Feminino , Fenclonina/farmacologia , Elevação dos Membros Posteriores/psicologia , Ketanserina/farmacologia , Masculino , Camundongos , Compostos Organosselênicos/química , Natação/psicologia
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