Laboratório de Neurociências, Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), and Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
Pharmacol Biochem Behav. 2012 Dec;103(2):395-402. doi: 10.1016/j.pbb.2012.09.018. Epub 2012 Oct 2.
Animal models of chronic stress represent valuable tools by which to investigate the behavioral, endocrine and neurobiological changes underlying stress-related psychopathologies, such as major depression, and the efficacy of antidepressant therapies. The present study was aimed at investigating the neurochemical effects of the antidepressant tianeptine in rats exposed to the chronic stress model. To this aim, rats were subjected to 40days of chronic unpredictable stressful stimuli, after which the animals received saline or tianeptine (15mg/kg) once a day for 7days. Additionally, IL-6, IL-1, TNF-α levels and oxidative stress parameters were assessed in the prefrontal cortex (PFC), hippocampus (HPC), amygdala (AMY) and nucleus accumbens (NAc) in all of the experimental groups studied. The results indicated that chronic mild stress and tianeptine did not exercise any effects on cytokines in all of the structures studied; in the PFC and AMY thiobarbituric acid reactive substances (TBARS) levels were decreased in control rats treated with tianeptine in the HPC; superoxide dismutase (SOD) activity was found to have decreased in stressed rats treated with saline in the PFC, HPC, AMY and NAc, and tianeptine reversed this effect; catalase (CAT) activity was found to have decreased in the PFC, HPC and NAc of stressed rats treated with saline, but was shown to have increased in stressed rats treated with tianeptine, and tianeptine also reversed the decreases in CAT activity in stressed rats treated with saline, suggesting that tianeptine exerted antioxidant activity. In conclusion, the present findings open new vistas on the pharmacological activity of tianeptine, in particular, concerning its ability to attenuate oxidative stress.
动物慢性应激模型是一种很有价值的工具,可以用来研究与应激相关的精神病理学(如重度抑郁症)的行为、内分泌和神经生物学变化,以及抗抑郁治疗的疗效。本研究旨在探讨抗抑郁药噻奈普汀对慢性应激模型大鼠的神经化学作用。为此,大鼠接受了 40 天的慢性不可预测的应激刺激,之后动物每天接受盐水或噻奈普汀(15mg/kg)一次,共 7 天。此外,还评估了所有实验组的前额叶皮质(PFC)、海马(HPC)、杏仁核(AMY)和伏隔核(NAc)中的白细胞介素 6(IL-6)、白细胞介素 1(IL-1)、肿瘤坏死因子-α(TNF-α)水平和氧化应激参数。结果表明,慢性轻度应激和噻奈普汀对所有研究结构中的细胞因子均无影响;在 PFC 和 AMY 中,用噻奈普汀处理的对照组大鼠的硫代巴比妥酸反应物质(TBARS)水平降低;在 PFC、HPC、AMY 和 NAc 中,用生理盐水处理的应激大鼠的超氧化物歧化酶(SOD)活性降低,噻奈普汀逆转了这一效应;在 PFC、HPC 和 NAc 中,用生理盐水处理的应激大鼠的过氧化氢酶(CAT)活性降低,但用噻奈普汀处理的应激大鼠的 CAT 活性增加,噻奈普汀还逆转了用生理盐水处理的应激大鼠的 CAT 活性降低,表明噻奈普汀具有抗氧化活性。总之,本研究结果为噻奈普汀的药理学活性开辟了新的视野,特别是其减轻氧化应激的能力。