Laboratory of Neuropharmacology, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil.
Brain Res Bull. 2010 Aug 30;83(1-2):9-15. doi: 10.1016/j.brainresbull.2010.05.011. Epub 2010 Jul 1.
A growing body of evidence has pointed to the ionotropic glutamate N-methyl-d-aspartate receptor (NMDA) as an important player in the etiology of psychopathologies, including anxiety and major depression. Clinical findings suggest that ketamine may be used for the treatment of major depression. There is evidence that reactive oxygen species also play an important role in the pathogenesis of many diseases, particularly those which are neurological and psychiatric in nature. This study examined the behavioral and oxidative stress alterations after a single administration of ketamine (5, 10 and 20mg/kg i.p.) in mice. Ketamine presented a significant anxiogenic effect in the elevated plus-maze model of anxiety, also increasing locomotor activity. In the forced swimming and tail suspension tests, a significant decrease in immobility time after ketamine administration was observed. In addition to the behavioral changes induced by ketamine, this drug also increased lipid peroxidation, nitrite content and catalase activity, while decreased GSH levels in mice prefrontal cortex. In conclusion, our results confirm the antidepressant effects of ketamine, also showing a pro-oxidant effect of this drug.
越来越多的证据表明，离子型谷氨酸 N-甲基-D-天冬氨酸受体（NMDA）在焦虑症和重度抑郁症等精神病理学的发病机制中起着重要作用。临床研究结果表明，氯胺酮可能可用于治疗重度抑郁症。有证据表明，活性氧也在许多疾病的发病机制中起着重要作用，特别是那些具有神经和精神疾病性质的疾病。本研究在小鼠中单次给予氯胺酮（5、10 和 20mg/kg 腹腔注射）后，观察了行为和氧化应激的改变。氯胺酮在焦虑的高架十字迷宫模型中呈现出明显的焦虑作用，同时也增加了运动活动。在强迫游泳和悬尾试验中，观察到氯胺酮给药后不动时间明显减少。除了氯胺酮引起的行为改变外，这种药物还增加了小鼠前额叶皮层的脂质过氧化、亚硝酸盐含量和过氧化氢酶活性，同时降低了 GSH 水平。总之，我们的结果证实了氯胺酮的抗抑郁作用，同时也显示了这种药物的促氧化作用。
