Center of Health Sciences, Department of Physiology and Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil; Center of Health Sciences, Postgraduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Center of Health Sciences, Department of Physiology and Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Behav Brain Res. 2020 Jun 18;388:112643. doi: 10.1016/j.bbr.2020.112643. Epub 2020 Apr 24.
Depression is one of the most common mood disorders, which affects one in six people at some point in life. However, the treatment of this disease is still a challenge. Chronic corticosterone administration (CCA) is a widely used animal model to study the mechanisms involved, as well as possible therapeutic strategies for the treatment of depression. Moreover, elevated oxidative stress has been observed in psychiatric disorders, including major depression and, in this context, antioxidant therapy may be a potential therapeutic alternative. In this study, we investigated the effect of seven days of treatment with apocynin, an antioxidant of natural origin, on depressive-like behavior and oxidative parameters in mice submitted to CCA. After 21 days of corticosterone administration (20 mg/Kg/day, subcutaneously, s.c.), we observed the development of depressive-like behavior with an increase in immobility time on tail suspension test and forced swimming test and reduction in total grooming time on splash test. Also, we found high superoxide dismutase activity and hydrogen peroxide levels whereas catalase activity was reduced in the prefrontal cortex, hippocampus and striatum. Seven days of treatment with apocynin (100 mg/Kg/day orally, p.o), performed immediately after corticosterone administration in the last week of protocol, was able to reverse the most of these changes, revealing its antidepressant-like effect. In conclusion, our results suggest apocynin as an antidepressant-like agent with a mechanism of action based on the attenuation of oxidative changes induced by CCA.
抑郁症是最常见的情绪障碍之一，一生中每六个人就有一人会受到影响。然而，这种疾病的治疗仍然是一个挑战。慢性皮质酮给药（CCA）是一种广泛用于研究相关机制以及治疗抑郁症的可能治疗策略的动物模型。此外，精神疾病中观察到氧化应激升高，包括重度抑郁症，在这种情况下，抗氧化治疗可能是一种潜在的治疗选择。在这项研究中，我们研究了抗氧化剂原花青素（apocynin）治疗七天对接受 CCA 的小鼠的抑郁样行为和氧化参数的影响。在 21 天的皮质酮给药（20mg/kg/天，皮下注射，s.c.）后，我们观察到抑郁样行为的发展，表现在悬尾试验和强迫游泳试验中不动时间增加，而飞溅试验中总梳理时间减少。此外，我们发现前额叶皮层、海马体和纹状体中超氧化物歧化酶活性和过氧化氢水平升高，而过氧化氢酶活性降低。在方案的最后一周，在给予皮质酮后立即进行七天的原花青素（100mg/kg/天口服，p.o）治疗，能够逆转其中大部分变化，显示其抗抑郁样作用。总之，我们的结果表明原花青素作为一种具有抗抑郁样作用的药物，其作用机制基于减轻 CCA 诱导的氧化变化。
