The selenium-containing compound 3-((4-chlorophenyl)selanyl) -1-methyl-1H-indole reverses depressive-like behavior induced by acute restraint stress in mice: modulation of oxido-nitrosative stress and inflammatory pathway Angela Maria Casaril 1,2 & Micaela Domingues 1 & Suely Ribeiro Bampi 1 & Darling de Andrade Lourenço 1 & Nathalia Batista Padilha 3 & Eder João Lenardão 3 & Mariana Sonego 4 & Fabiana Kommling Seixas 4 & Tiago Collares 4 & Cristina Wayne Nogueira 5 & Robert Dantzer 2 & Lucielli Savegnago 1 Received: 21 August 2018 / Accepted: 11 December 2018 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Rationale and objectives Stress-induced alterations in oxidative and inflammatory parameters have been implicated in the pathophysiology of mood disorders. Based on the antioxidant and anti-inflammatory properties of the selenium-containing compound 3-((4-chlorophenyl)selanyl)-1-methyl-1H-indole (CMI), we assessed its ability to reverse depression-like behavioral alterations, neuroinflammation, and oxidative imbalance induced by acute restraint stress. Methods Mice submitted to restraint for 240 min received CMI (1 or 10 mg/kg, orally) 10 min after the end of the stress induction. Behavioral and biochemical tests were carried out after further 30 min. Results Restraint-induced depression-like behavior in the tail suspension test (TST), splash test, and new object exploration test was reversed by CMI. None of the treatments evoked locomotor alteration. In addition, CMI abrogated restraint-induced increases in plasma levels of corticosterone and in markers of oxidative stress and impaired superoxide dismutase and catalase activity in the prefrontal cortex (PFC) and hippocampus (HC). CMI also blocked stress-induced downregulation of mRNA levels of glucocorticoid receptor and brain-derived neurotrophic factor and upregulation of nuclear factor kappa B, inducible nitric oxide synthase, tumor necrosis alpha, indoelamine-2,3-dioxygenase, and glycogen synthase kinase 3 beta in PFC and HC. Conclusions These preclinical results indicate that administration of selenium-containing compounds might help to treat depres- sion associated with inflammation and oxidative stress. Keywords Antidepressant . Selenium . Acute restraint stress . Oxidative stress . Neuroinflammation Angela Maria Casaril and Micaela Domingues contributed equally to this work. This article belongs to a Special Issue on Neuroimmune Signaling in Psychiatric Disease * Lucielli Savegnago luciellisavegnago@yahoo.com.br 1 Centro de Desenvolvimento Tecnológico, Unidade de Biotecnologia, Grupo de Pesquisa em Neurobiotecnologia, Universidade Federal de Pelotas, Pelotas, RS 96010-900, Brazil 2 Division of Internal Medicine, Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 3 Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Laboratório de Síntese Orgânica Limpa, Universidade Federal de Pelotas, Pelotas, RS, Brazil 4 Centro de Desenvolvimento Tecnológico, Unidade de Biotecnologia, Grupo de Pesquisa em Oncologia Celular e Molecular, Laboratório de Genômica Funcional, Universidade Federal de Pelotas, Pelotas, RS, Brazil 5 Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil Psychopharmacology https://doi.org/10.1007/s00213-018-5151-x