Chakraborti Ayanabha, Gulati Kavita, Ray Arunabha
Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, India.
Behav Brain Res. 2008 Dec 1;194(1):86-91. doi: 10.1016/j.bbr.2008.06.027. Epub 2008 Jul 3.
The effect of restraint stress (RS) on neurobehavioral and brain oxidative/nitrosative stress markers and their modulation by antioxidants and nitrergic agents were evaluated in young (2 months) and old (16 months) male Wistar rats. Exposure to RS, induced anxiogenesis when tested in the elevated plus maze (EPM) and open field (OF) tests and such changes were greater in the old as compared to the young rats. These behavioral alterations were associated with enhanced levels of malondialdehyde (MDA) and reductions in glutathione (GSH), catalase (CAT) and nitric oxide metabolites (NOx) levels in brain homogenates-the effects being greater in intensity in the old as compared to the young animals. Pretreatment with antioxidants, alpha-tocopherol (25 and 50mg/kg) and N-acetylcysteine (100 and 200mg/kg) consistently reversed the RS-induced behavioral and biochemical alterations in both young and old rats. Similar attenuations of RS-induced changes were seen after pretreatment with NO precursor L-arginine (500 and 1000mg/kg) while the NO synthase inhibitor N-nitro L-arginine methyl ester (L-NAME) (50 and 100mg/kg) tended to aggravate the effects of RS in both age groups of rats. The results suggest that susceptibility to stress-induced neurobehavioral alterations may increase with age and interactions of reactive oxygen species (ROS) and nitric oxide in the central nervous system may exert a regulatory influence in such age dependent responses to stress.
在年轻（2个月）和老年（16个月）雄性Wistar大鼠中，评估了束缚应激（RS）对神经行为和脑氧化/亚硝化应激标志物的影响，以及抗氧化剂和氮能药物对它们的调节作用。在高架十字迷宫（EPM）和旷场（OF）试验中测试时，暴露于RS会诱发焦虑，与年轻大鼠相比，老年大鼠的这种变化更大。这些行为改变与脑匀浆中丙二醛（MDA）水平升高以及谷胱甘肽（GSH）、过氧化氢酶（CAT）和一氧化氮代谢产物（NOx）水平降低有关，与年轻动物相比，老年动物的这些影响强度更大。用抗氧化剂α-生育酚（25和50mg/kg）和N-乙酰半胱氨酸（100和200mg/kg）预处理可一致逆转RS诱导的年轻和老年大鼠的行为和生化改变。在用NO前体L-精氨酸（500和1000mg/kg）预处理后，也观察到RS诱导的变化有类似的减轻，而NO合酶抑制剂N-硝基-L-精氨酸甲酯（L-NAME）（50和100mg/kg）在两个年龄组的大鼠中都倾向于加重RS的影响。结果表明，对应激诱导的神经行为改变的易感性可能随年龄增加，并且中枢神经系统中活性氧（ROS）和一氧化氮的相互作用可能在这种年龄依赖性应激反应中发挥调节作用。
