Lamotrigine blocks apoptosis induced by repeated administration of high-dose methamphetamine in the medial prefrontal cortex of rats
Lamotrigine blocks apoptosis induced by repeated administration of high-dose methamphetamine in the medial prefrontal cortex of rats
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DOI：
10.1016/j.neulet.2010.11.028
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发表时间：
2011-03-03
影响因子：
2.5
通讯作者：
Koyama, Tsukasa
中科院分区：
文献类型：
--
作者：
Nakato, Yasuya;Abekawa, Tomohiro;Koyama, Tsukasa
拉莫三嗪（LTG）有时与抗精神病药物合用，用于治疗精神分裂症。然而，LTG用于精神分裂症的药理学基础尚未报道。我们小组最近提出了一种新的精神兴奋剂动物模型，可能反映了精神分裂症的进行性病理生理学。使用该模型获得的结果显示，LTG阻断大鼠中重复高剂量甲基苯丙胺诱导的前脉冲抑制缺陷的起始和表达（Nakato等人，2010，Neurosci. Lett. [25]）。使用该模型，LTG（30 mg/kg）对甲基苯丙胺（METH，2.5 mg/kg）诱导的内侧前额叶皮层（mPFC）细胞外谷氨酸水平增加的影响在本研究中进行了检查。然后研究重复共同施用LTG（30 mg/kg）对重复METH（2.5 mg/kg）诱导的大鼠该区域细胞凋亡的影响。结果显示LTG（30 mg/kg）阻断METH（2.5 mg/kg）诱导的mPFC中谷氨酸增加。LTG（30 mg/kg）的重复联合给药阻断了mPFC中METH（2.5 mg/kg）重复给药诱导的细胞凋亡的发生。LTG阻断由重复给予METH诱导的组织学异常，这表明LTG的机制可以防止精神分裂症的进行性病理生理学。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Lamotrigine (LTG) is sometimes co-administered with antipsychotic drugs for the treatment of schizophrenia. Nevertheless, the pharmacological basis of LTG use for schizophrenia has not been reported. Our group recently proposed a new psychostimulant animal model that might reflect the progressive pathophysiology of schizophrenia. Results obtained using that model show that LTG blocks the initiation and expression of repeated high-dosage methamphetamine-induced prepulse inhibition deficit in rats (Nakato et al., 2010, Neurosci. Lett. [25]). Using the model, the effect of LTG (30 mg/kg) on methamphetamine (METH, 2.5 mg/kg)-induced increases in extracellular glutamate levels in the medial prefrontal cortex (mPFC) was examined in this study. Then the effect of repeated co-administration of LTG (30 mg/kg) on repeated METH (2.5 mg/kg)-induced apoptosis in this region of rats was investigated. Results show that LTG (30 mg/kg) blocked the METH (2.5 mg/kg)-induced glutamate increase in the mPFC. Repeated co-administration of LTG (30 mg/kg) blocked the development of apoptosis induced by repeated administration of METH (2.5 mg/kg) in the mPFC. The LTG blocks histological abnormalities induced by repeated administration of METH, which suggests a mechanism of LTG that protects against progressive pathophysiology in schizophrenia. (C) 2010 Elsevier Ireland Ltd. All rights reserved.