Shalaby Amany, Kamal Sahar
Int J Physiol Pathophysiol Pharmacol. 2009 Jun 20;1(2):154-161.
Oxidative stress is a critical route of damage in various psychological stress-induced disorders, such as depression. Antidepressants are widely prescribed to treat these conditions; however, few animal studies have investigated the effect of these drugs on endogenous antioxidant status in the brain. The present study employed a 3 weeks chronic regimen of random exposure to chronic mild stress (CMS) to induce oxidative stress in brain, and behavioural aberrations (anhedonia), in rats. The sucrose preference test was used to identify depression-like phenotypes, and reversal in these indices indicated the effectiveness of treatment with escitalopram 2.5mg/kg daily orally following CMS. The level of superoxide dismutase enzyme(SOD) as an antioxidant markers in erythrocyte lysates was reduced in CMS control group while it was elevated in CMS group treated with escitalopram. Also escitalopram significantly reduce the thiobarbituric acid reactive substance(TBARS) levels in selected brain areas homogenates to a level comparable to control group. Catalase activity and GABA levels in these brain areas were also increase in escitlopram treated group. In conclusion, escitalopram is suggested to have antioxidant effect associated with an increase in GABA level in frontal cortices and nucleus accumbens homogenates from rats exposed to CMS.
氧化应激是各种心理应激诱导的疾病(如抑郁症)中损伤的关键途径。抗抑郁药被广泛用于治疗这些疾病;然而,很少有动物研究调查这些药物对大脑内源性抗氧化状态的影响。本研究采用3周的慢性随机暴露于慢性轻度应激(CMS)方案,以诱导大鼠大脑中的氧化应激和行为异常(快感缺失)。蔗糖偏好试验用于识别类似抑郁的表型,这些指标的逆转表明每天口服2.5mg/kg艾司西酞普兰治疗CMS后有效。在CMS对照组中,作为红细胞裂解物中抗氧化标志物的超氧化物歧化酶(SOD)水平降低,而在用艾司西酞普兰治疗的CMS组中升高。此外,艾司西酞普兰显著降低所选脑区匀浆中的硫代巴比妥酸反应物质(TBARS)水平,使其与对照组相当。在这些脑区中,过氧化氢酶活性和GABA水平在用艾司西酞普兰治疗的组中也增加。总之,提示艾司西酞普兰具有抗氧化作用,这与暴露于CMS的大鼠额叶皮质和伏隔核匀浆中GABA水平的增加有关。