Sodium- and magnesium-valproate in vivo modulate glutamatergic and GABAergic synapses in the medial prefrontal cortex
Sodium- and magnesium-valproate in vivo modulate glutamatergic and GABAergic synapses in the medial prefrontal cortex
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DOI：
10.1007/s00213-006-0317-3
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发表时间：
2006-04-01
影响因子：
3.4
通讯作者：
Janiri, L
中科院分区：
文献类型：
--
作者：
Gobbi, G;Janiri, L
理由：丙戊酸（VPA）是一种精神活性药物，目前用于治疗癫痫。最近，它已被引入精神病学，用于治疗双相情感障碍、攻击性、冲动性和顽固性精神分裂症，尽管VPA作用于这些精神疾病的机制尚不清楚。目的：分析丙戊酸钠（Na-）和丙戊酸镁（Mg-VPA）对内侧前额叶皮层（mPFC）锥体神经元的不同作用及其与γ -氨基丁酸（GABA）和兴奋性氨基酸反应的相互作用。材料和方法：采用体内电生理和微离子电泳技术来实现这些目标。结果：两种VPA盐降低了超过60%的锥体神经元的自发神经元放电活性，并增强了GABA的抑制作用。Mg-VPA比Na-VPA更能阻断n -甲基- d -天冬氨酸（NMDA）诱导的兴奋性反应。两种VPA盐同样阻断了准钠酸盐和盐酸盐的兴奋反应。结论：VPA盐可显著调节mPFC锥体神经元兴奋性氨基酸的活性，这一机制可以解释丙戊酸盐在mPFC水平上对NMDA、AMPA和kainate受体相关精神疾病的治疗作用。
Rationale: Valproic acid (VPA) is a psychoactive drug currently used for the treatment of epilepsy. Recently it has been introduced in psychiatry for the treatment of bipolar disorders, aggression, impulsivity, and resistant schizophrenia, although the mechanism by which VPA acts on these psychiatric diseases remains still unknown. Objectives: The aim of this study was to analyze the distinct effects of sodium-(Na-) and magnesium-valproate (Mg-VPA) in pyramidal neurons of the medial prefrontal cortex (mPFC) and their interactions with gamma-aminobutyric acid (GABA) and excitatory amino acid responses. Materials and methods: In vivo electrophysiology and microiontophoresis techniques were used to attend these goals. Results: Both VPA salts decreased spontaneous neuronal firing activity in greater than 60% of recorded pyramidal neurons as well as potentiated GABA inhibitions. When injected at equal concentrations and currents, Mg-VPA blocked the excitatory responses induced by N-methyl-D-aspartate (NMDA) more frequently than Na-VPA. Both VPA salts equally blocked the excitatory responses of quisqualate and kainate. Conclusions: These data suggest that VPA salts significantly modulate the activity of excitatory amino acid at mPFC pyramidal neurons and this mechanism should explain the therapeutic effects of valproate in psychiatric diseases involving NMDA, AMPA, and kainate receptors at the mPFC level.