title: The protective effect of melatonin against brain oxidative stress and hyperlocomotion in a rat model of mania induced by ouabain.
abstract: This study was designed to investigate the protective effect of melatonin in a preclinical animal model of mania induced by ouabain (OUA). Male Wistar rats were pretreated with melatonin (5 or 20mg/kg; intraperitoneal, i.p.) for seven days or with the mood stabilizer lithium chloride (positive control) (45 mg/kg, per oral, p.o.). One day after the last dose, animals received an intracerebroventricular (i.c.v.) injection of OUA (5μl, 10(-5)M), a Na(+)K(+)ATPase-inhibiting compound. Locomotor activity was assessed in the open-field test (OFT). The levels of reactive species (RS), protein carbonyl (PC) and non-protein thiols (NPSH), as well as the activities of the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measured in the cerebral cortex and hippocampus of rats. OUA markedly increased the locomotor activity in the OFT, and the pretreatment with melatonin or lithium chloride prevented this effect. Melatonin treatment (similar to lithium) was also effective in preventing the following alterations elicited by OUA: increase of RS and PC levels; depletion of NPSH levels; increase of SOD activity; and inhibition of CAT and GPx activities. Moreover, we found that brain oxidative stress and behavioural alterations elicited by OUA were significantly correlated. Our study showed that Melatonin, similarly to lithium, protected against OUA-induced brain oxidative stress and hyperlocomotion in rats. Thus, our findings reinforce the notion that oxidative stress may play an important role in the manic-like behavioural. Therefore, we indicate that melatonin has antimanic-like action, suggesting a potential role for this substance in the pharmacological management of Bipolar disorder.
authors: Programa de Pós-graduação em Bioquímica (PPGBioq)-Universidade Federal do Pampa (Unipampa), Campus Uruguaiana, BR 472 KM 582, Caixa Postal 118, CEP 97500-970 Uruguaiana, RS, Brazil; Laboratório de avaliações farmacológicas e toxicológicas aplicadas às moléculas bioativas (LaftamBio)-Universidade Federal do Pampa (Unipampa), Rua Luiz Joaquim de Sá Britto, s/n, Campus Itaqui-, CEP 97650-000 Itaqui, RS, Brazil.
authors: Leandro C
authors: LC
authors: Souza
authors: Laboratório de síntese, reatividade e avaliações farmacológicas e toxicológicas de organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CEP 97105-900 Santa Maria, RS, Brazil.
authors: Ethel Antunes
authors: EA
authors: Wilhelm
authors: Laboratório de síntese, reatividade e avaliações farmacológicas e toxicológicas de organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CEP 97105-900 Santa Maria, RS, Brazil.
authors: Cristiani Folharini
authors: CF
authors: Bortolatto
authors: Laboratório de síntese, reatividade e avaliações farmacológicas e toxicológicas de organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CEP 97105-900 Santa Maria, RS, Brazil.
authors: Cristina Wayne
authors: CW
authors: Nogueira
authors: Laboratório de avaliações farmacológicas e toxicológicas aplicadas às moléculas bioativas (LaftamBio)-Universidade Federal do Pampa (Unipampa), Rua Luiz Joaquim de Sá Britto, s/n, Campus Itaqui-, CEP 97650-000 Itaqui, RS, Brazil.
authors: Silvana P
authors: SP
authors: Boeira
authors: Programa de Pós-graduação em Bioquímica (PPGBioq)-Universidade Federal do Pampa (Unipampa), Campus Uruguaiana, BR 472 KM 582, Caixa Postal 118, CEP 97500-970 Uruguaiana, RS, Brazil; Laboratório de avaliações farmacológicas e toxicológicas aplicadas às moléculas bioativas (LaftamBio)-Universidade Federal do Pampa (Unipampa), Rua Luiz Joaquim de Sá Britto, s/n, Campus Itaqui-, CEP 97650-000 Itaqui, RS, Brazil. Electronic address: cristianoricardojesse@yahoo.com.br.
authors: Cristiano R
authors: CR
authors: Jesse
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D001714:Bipolar Disorder / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D002374:Catalase / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010042:Ouabain; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D018692:Antimanic Agents; D018696:Neuroprotective Agents; D010042:Ouabain; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D018021:Lithium Chloride; D008550:Melatonin
keywords: Bipolar disorder; Melatonin; Ouabain; Oxidative stress