Ignácio Zuleide M, Réus Gislaine Z, Abelaira Helena M, de Moura Airam B, de Souza Thays G, Matos Danyela, Goldim Mariana P, Mathias Khiany, Garbossa Leandro, Petronilho Fabricia, Quevedo João
Laboratório de Neurociências, Unidade Acadêmica em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Laboratório de Fisiologia, Farmacologia e Psicopatologia, Campus Chapecó, Universidade Federal da Fronteira Sul, Chapecó, Santa Catarina, Brazil.
Metab Brain Dis. 2017 Aug;32(4):1195-1208. doi: 10.1007/s11011-017-0028-y. Epub 2017 May 6.
Many studies note that changes in oxidative balance are involved in the pathogenesis of major depressive disorder (MDD) and in the success of some antidepressants. Quetiapine exerts a therapeutic response and induces changes in physiological mechanisms that appear to underlie MDD. The objective of this study was to evaluate the antidepressant and antioxidant effects of quetiapine (20 mg /kg) in adult animals. Sixty minutes after an acute treatment or the last administration of chronic treatment (14 days) with quetiapine, animals were subjected to the forced swimming test (FST) to evaluate mobility parameters. Then, the hippocampus, prefrontal cortex (CPF), amygdala and nucleus accumbens (NAc) were removed for the assessment of oxidative stress parameters. Both acute and chronic treatments exerted antidepressant-like effects. Myeloperoxidase (MPO) activity was reduced in the amygdala after acute treatment and in the hippocampus, PFC and amygdala after chronic treatment. In addition, after chronic treatment, the levels of thiobarbituric reactive species (TBARS) were reduced in the amygdala and NAc, and the protein carbonyl content was reduced in the CPF. Superoxide dismutase (SOD) activity increased in the NAc after acute and chronic treatments. Catalase (CAT) activity increased in the PFC after acute treatment and in the NAc after acute and chronic treatments. The concentration of nitrite/nitrate was lower in the CPF after chronic treatment. These results corroborate the antidepressant effect of quetiapine and indicate that quetiapine exhibits an antioxidant profile, a physiological mechanism that appears be involved in the therapeutic function of quetiapine in individuals resistant to classical antidepressant treatments.
许多研究指出，氧化平衡的变化与重度抑郁症（MDD）的发病机制以及某些抗抑郁药的疗效有关。喹硫平具有治疗反应，并能诱导一些似乎是MDD基础的生理机制发生变化。本研究的目的是评估喹硫平（20毫克/千克）对成年动物的抗抑郁和抗氧化作用。在用喹硫平进行急性治疗或慢性治疗（14天）的最后一次给药60分钟后，对动物进行强迫游泳试验（FST）以评估活动参数。然后，取出海马体、前额叶皮质（CPF）、杏仁核和伏隔核（NAc）以评估氧化应激参数。急性和慢性治疗均产生了抗抑郁样作用。急性治疗后杏仁核中的髓过氧化物酶（MPO）活性降低，慢性治疗后海马体、前额叶皮质和杏仁核中的MPO活性降低。此外，慢性治疗后，杏仁核和NAc中的硫代巴比妥酸反应性物质（TBARS）水平降低，CPF中的蛋白质羰基含量降低。急性和慢性治疗后，NAc中的超氧化物歧化酶（SOD）活性增加。急性治疗后PFC中的过氧化氢酶（CAT）活性增加，急性和慢性治疗后NAc中的CAT活性增加。慢性治疗后CPF中的亚硝酸盐/硝酸盐浓度较低。这些结果证实了喹硫平的抗抑郁作用，并表明喹硫平具有抗氧化特性，这一生理机制似乎参与了喹硫平在对经典抗抑郁治疗耐药个体中的治疗功能。
