title: Diphenyl diselenide ameliorates behavioral and oxidative parameters in an animal model of mania induced by ouabain.
abstract: Bipolar disorder (BD) is a common and severe mood disorder associated with higher rates of suicide and disability. Ouabain, a Na(+)/K(+)-ATPase inhibitor, induces behavioral changes in rats and has been used as a model of mania. The aim of this study was to investigate if diphenyl diselenide [(PhSe)(2)], an organoselenium compound with pharmacological properties, is effective against ouabain-induced hyperactivity and alterations in cerebral oxidative status of rats. Male Wistar rats were treated with a single dose of (PhSe)(2) (50 mg/kg, p.o.) 30 min before i.c.v. injection of ouabain (5 μl, 10(-5) M) or with the mood stabilizer, lithium chloride (LiCl) (45 mg/kg, p.o.), twice a day, for 7 days before the administration of ouabain. Open-field locomotion was quantified after ouabain administration. Thiobarbituric acid reactive substances (TBARS), oxidatively modified proteins, tyrosine nitration, ascorbic acid and non-protein thiols (NPSH) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities were determined in the whole brain. Ouabain increased locomotor activity in the open-field test and pretreatment with (PhSe)(2) or LiCl blocked this effect. In addition, ouabain increased lipid peroxidation and oxidatively modified proteins, demonstrated by a significant increase in TBARS levels and carbonyl content, which were attenuated by pretreatment with (PhSe)(2) or LiCl. The activities of SOD and CAT were increased by ouabain. LiCl was effective on preventing the increases of both enzyme activities, but (PhSe)(2) attenuated the ouabain effect in SOD activity. GPx and GR activities, ascorbic acid, NPSH and tyrosine nitration levels were not altered in all experimental groups. Similarly to LiCl, (PhSe)(2) produced an antimanic-like action, since it was effective against the locomotor hyperactivity elicited by ouabain. The results also indicated that (PhSe)(2) was effective against oxidative stress caused by ouabain in rats.
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
authors.forename: César Augusto
authors.initials: CA
authors.lastname: Brüning
authors.forename: Marina
authors.initials: M
authors.lastname: Prigol
authors.forename: Cristiane
authors.initials: C
authors.lastname: Luchese
authors.forename: Simone
authors.initials: S
authors.lastname: Pinton
authors.forename: Cristina Wayne
authors.initials: CW
authors.lastname: Nogueira
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001555:Benzene Derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016566:Organoselenium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D010042:Ouabain; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D001555:Benzene Derivatives; D016566:Organoselenium Compounds; D017392:Thiobarbituric Acid Reactive Substances; C061132:diphenyldiselenide; D010042:Ouabain; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase