title: 7-Fluoro-1,3-diphenylisoquinoline-1-amine abolishes depressive-like behavior and prefrontal cortical oxidative damage induced by acute restraint stress in mice.
abstract: There is a complex relationship between stressful situations and the onset of depression. 7-Fluoro-1,3-diphenylisoquinoline-1-amine (FDPI) has been reported to have an antidepressant-like effect in the forced swimming test (FST). The aim of this study was to investigate the antidepressant-like effect of FDPI administered to mice before or after the acute restraint stress (ARS). The mice were submitted to the ARS for 7 h. Two treatments with FDPI (10 mg/kg) were performed: in the first treatment, the mice received FDPI 30 min before ARS (pre-treatment) and in the second treatment mice received FDPI 10 min after the ARS (post-treatment). Thirty minutes after FDPI administration, the FST and locomotor activity were carried out. ARS induced depressive-like behavior in the FST. Both treatments with FDPI were effective against the increase in immobility time in the FST.Moreover, ARS increased lipid peroxidation and intracellular reactive oxygen species (ROS) levels as well as decreased catalase activity in prefrontal cortical samples of mice. Pre- and post-treatments with FDPI reduced lipid peroxidation and ROS, and post-treatment restored catalase activity. Superoxide dismutase was not altered by stress and/or FDPI. Monoamine oxidase (MAO) activities increased in the prefrontal-cortices of mice submitted to the ARS protocol and treatments with FDPI abolished this increase. Hepatic MAO activities were not altered in the livers of mice submitted to ARS and FDPI treatments. The serotonin uptake was increased in the prefrontal-cortices of mice submitted to the ARS protocol and both treatments with FDPI abolished this increase. The antidepressant-like effect of FDPI appears to involve the modulation of oxidative stress and the monoaminergic system, without inhibiting hepatic MAO activity.
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CEP 97105-900 Santa Maria, Rio Grande do Sul, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Pesarico
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CEP 97105-900 Santa Maria, Rio Grande do Sul, Brazil.
authors.forename: Eluza Curte
authors.initials: EC
authors.lastname: Stangherlin
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CEP 97105-900 Santa Maria, Rio Grande do Sul, Brazil.
authors.forename: Anderson C
authors.initials: AC
authors.lastname: Mantovani
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CEP 97105-900 Santa Maria, Rio Grande do Sul, Brazil.
authors.forename: Gilson
authors.initials: G
authors.lastname: Zeni
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CEP 97105-900 Santa Maria, Rio Grande do Sul, Brazil. Electronic address: criswn@ufsm.br.
authors.forename: Cristina Wayne
authors.initials: CW
authors.lastname: Nogueira
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology*; D002374:Catalase; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism; D017397:Prefrontal Cortex / Q000503:physiopathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012149:Restraint, Physical; D012701:Serotonin / Q000378:metabolism; D013482:Superoxide Dismutase; D013550:Swimming / Q000523:psychology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D007546:Isoquinolines; D017382:Reactive Oxygen Species; D014316:Tritium; D012701:Serotonin; D002374:Catalase; D013482:Superoxide Dismutase; D008995:Monoamine Oxidase
keywords: Antioxidant; Depression; Isoquinoline; Monoaminergic system; Stress