Biggs C S, Pearce B R, Fowler L J, Whitton P S
Department of Pharmacology, School of Pharmacy, London, UK.
Brain Res. 1992 Oct 23;594(1):138-42. doi: 10.1016/0006-8993(92)91038-g.
We report the effects of i.p. administration of sodium valproate (VPA) on extracellular concentrations of various amino acids in the rat ventral hippocampus studied using in vivo microdialysis, followed by HPLC with fluorometric detection. At the doses used (100, 200 and 400 mg/kg), VPA had no effect on extracellular aspartate, glutamine and taurine, whilst inducing a small, but not statistically significant increase in glutamate at 200 and 400 mg/kg. In contrast, VPA administration produced a biphasic effect on extracellular GABA levels which was dependent on the dose used. At 100 mg/kg, VPA reduced GABA concentrations by 50% when compared to basal. 200 mg/kg VPA had virtually no effect, whilst 400 mg/kg VPA raised extracellular GABA levels to 200% of basal. The results are discussed in relation to the known pharmacological and anticonvulsant actions of VPA.
我们报告了腹腔注射丙戊酸钠(VPA)对大鼠腹侧海马体中各种氨基酸细胞外浓度的影响,该研究采用体内微透析技术,随后进行带荧光检测的高效液相色谱分析。在所使用的剂量(100、200和400mg/kg)下,VPA对细胞外天冬氨酸、谷氨酰胺和牛磺酸没有影响,而在200和400mg/kg时会使谷氨酸有小幅增加,但无统计学意义。相比之下,VPA给药对细胞外GABA水平产生了双相效应,这取决于所使用的剂量。与基础水平相比,100mg/kg的VPA使GABA浓度降低了50%。200mg/kg的VPA几乎没有影响,而400mg/kg的VPA使细胞外GABA水平提高到基础水平的200%。结合VPA已知的药理作用和抗惊厥作用对结果进行了讨论。