Corrêa Cristiane, Amboni Graziela, Assis Lara Clemes, Martins Márcio R, Kapczinski Flávio, Streck Emilio L, Quevedo João
Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2007 May 9;31(4):887-91. doi: 10.1016/j.pnpbp.2007.02.005. Epub 2007 Feb 15.
Some studies suggest that mitochondrial dysfunction may be related to the pathophysiology of bipolar disorder. In this work, we evaluated the activity of citrate synthase in rats, and the effects of the treatment with mood stabilizers (lithium and valproate) on the enzyme activity. In the first experiment (reversal treatment), amphetamine or saline were administered to rats for 14 days, and between day 8 and 14, rats were treated with either lithium, valproate or saline. In the second experiment (prevention treatment), rats were pretreated with lithium, valproate or saline, and between day 8 and 14, rats were administered amphetamine or saline. In reversal and prevention models, amphetamine administration significantly inhibited citrate synthase activity in rat hippocampus. In amphetamine-pretreated animals, valproate administration reversed citrate synthase activity inhibition induced by amphetamine. In the prevention model, pretreatment with lithium prevented amphetamine-induced citrate synthase inhibition. Our results showed that amphetamine inhibited citrate synthase activity and that valproate reversed and lithium prevented the enzyme inhibition.
一些研究表明，线粒体功能障碍可能与双相情感障碍的病理生理学有关。在这项研究中，我们评估了大鼠体内柠檬酸合酶的活性，以及心境稳定剂（锂盐和丙戊酸盐）治疗对该酶活性的影响。在第一个实验（逆转治疗）中，给大鼠注射苯丙胺或生理盐水，持续14天，在第8天至14天期间，给大鼠分别注射锂盐、丙戊酸盐或生理盐水。在第二个实验（预防治疗）中，先给大鼠注射锂盐、丙戊酸盐或生理盐水进行预处理，在第8天至14天期间，给大鼠注射苯丙胺或生理盐水。在逆转和预防模型中，注射苯丙胺显著抑制了大鼠海马体中柠檬酸合酶的活性。在预先用苯丙胺处理的动物中，注射丙戊酸盐可逆转苯丙胺诱导的柠檬酸合酶活性抑制。在预防模型中，锂盐预处理可预防苯丙胺诱导的柠檬酸合酶抑制。我们的结果表明，苯丙胺抑制柠檬酸合酶活性，丙戊酸盐可逆转该抑制作用，而锂盐可预防该酶的抑制。
