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

• Published in: Psychopharmacology Vol. 236; no. 10; pp. 2867 - 2880
• Main Authors: Casaril, Angela Maria, Domingues, Micaela, Bampi, Suely Ribeiro, de Andrade Lourenço, Darling, Padilha, Nathalia Batista, Lenardão, Eder João, Sonego, Mariana, Seixas, Fabiana Kommling, Collares, Tiago, Nogueira, Cristina Wayne, Dantzer, Robert, Savegnago, Lucielli
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2019; Springer Nature B.V
• Subjects: Animals; Anti-inflammatory agents; Antioxidants; Antioxidants - pharmacology; Antioxidants - therapeutic use; Behavior; Biochemical tests; Biomedical and Life Sciences; Biomedicine; Brain-derived neurotrophic factor; Catalase; Corticosterone; Depression - drug therapy; Depression - metabolism; Depression - psychology; Dioxygenase; Glucocorticoids; Glycogen; Glycogen synthase kinase 3; Indoles; Indoles - chemistry; Indoles - pharmacology; Indoles - therapeutic use; Inflammation; Inflammation - drug therapy; Inflammation - psychology; Male; Mental depression; Mice; Mood; mRNA; Neurosciences; Nitric oxide; Nitric-oxide synthase; Nitrosative Stress - drug effects; Nitrosative Stress - physiology; Original Investigation; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Pharmacology/Toxicology; Plasma levels; Prefrontal cortex; Psychiatry; Random Allocation; Restraint, Physical - methods; Restraint, Physical - psychology; Selenium; Selenium Compounds - chemistry; Selenium Compounds - pharmacology; Selenium Compounds - therapeutic use; Signal Transduction - drug effects; Signal Transduction - physiology; Stress, Psychological - drug therapy; Stress, Psychological - metabolism; Stress, Psychological - psychology; Superoxide dismutase; Antidepressant; Oxidative stress; Neuroinflammation; Acute restraint stress; Selenium
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-018-5151-x

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-1 H -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 depression associated with inflammation and oxidative stress. Graphical abstract ᅟ