Lithium and valproate modulate energy metabolism in an animal model of mania induced by methamphetamine
Lithium and valproate modulate energy metabolism in an animal model of mania induced by methamphetamine
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DOI：
10.1016/j.pbb.2012.09.010
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发表时间：
2013-01-01
影响因子：
3.6
通讯作者：
Quevedo, Joao
中科院分区：
文献类型：
--
作者：
Feier, Gustavo;Valvassori, Samira S.;Quevedo, Joao
研究表明双相情感障碍（BD）患者的线粒体复合物发生了改变。然而，对克雷布斯循环酶的变化研究很少。苯丙胺诱发的躁狂症动物模型已广泛用于双相躁狂症的研究。本研究的目的是评估由甲基苯丙胺（m-AMPH）诱导的躁狂症动物模型的行为和能量代谢的变化。首先给予Wistar大鼠m-AMPH或生理盐水14天，然后在第8天至第14天之间，给予大鼠锂（Li）、丙戊酸盐（VPA）或生理盐水（Sal）。使用旷场任务和克雷布斯循环酶（柠檬酸合酶和琥珀酸脱氢酶），线粒体呼吸链复合物（I，II，III和IV）和肌酸激酶在脑结构（前额叶，杏仁核，海马和纹状体）中测量的活动来评估运动行为。Li和VPA逆转m-AMPH诱导的多动症。管理的m-AMPH抑制克雷布斯循环酶和线粒体呼吸链的复合物在所有分析的结构的活动。Li和VPA逆转m-AMPH诱导的能量代谢功能障碍;然而，Li和VPA的作用依赖于所分析的脑区域。结果表明，m-AMPH诱导的Krebs循环酶活性降低可能是通过抑制线粒体呼吸链复合体而实现的。因此，克雷布斯循环酶的变化也可能参与BD。(c)2012年由Elsevier Inc.出版
Studies have shown alterations in mitochondrial complexes of bipolar disorder (BD) patients. However, changes in the Krebs cycle enzymes have been little studied. The animal model of mania induced by amphetamine has been widely used for the study of bipolar mania. The aim of this study is to assess behavioral and energy metabolism changes in an animal model of mania induced by methamphetamine (m-AMPH). Wistar rats were first given m-AMPH or saline for 14 days, and then, between days 8 and 14, rats were treated with lithium (Li), valproate (VPA), or saline (Sal). Locomotor behavior was assessed using the open-field task and activities of Krebs cycle enzymes (citrate synthase and succinate dehydrogenase), mitochondrial respiratory chain complexes (I, II, III, and IV), and creatine kinase measured in the brain structures (prefrontal, amygdala, hippocampus, and striatum). Li and VPA reversed m-AMPH-induced hyperactivity. The administration of m-AMPH inhibited the activities of Krebs cycle enzymes and complexes of the mitochondrial respiratory chain in all analyzed structures. Li and VPA reversed m-AMPH-induced energetic metabolism dysfunction; however, the effects of Li and VPA were dependent on the brain region analyzed. From the results obtained in this study, we suggested that the decreased Krebs cycle enzymes activity induced by m-AMPH may be inhibiting mitochondrial respiratory chain complexes. Therefore, changes in the Krebs cycle enzymes may also be involved in BD. (c) 2012 Published by Elsevier Inc.