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慢性给予丙戊酸可导致大鼠纹状体谷氨酸和牛磺酸水平降低。

Chronic administration of valproic acid induces a decrease in rat striatal glutamate and taurine levels.

机构信息

Instituto de Investigaciones Farmacológicas (ININFA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Junín 956, 5° piso, 1113, Buenos Aires, Argentina.

出版信息

Amino Acids. 1996 Jun;10(2):123-31. doi: 10.1007/BF00806585.

DOI:10.1007/BF00806585
PMID:24178474
Abstract

The effect of acute and chronic (10 days) administration of 200 mg/kg (i.p.) of valproic acid (VPA) on endogenous levels of aspartate, glutamate, alanine, glycine and taurine in the cerebral frontal cortex and corpus striatum of rats was studied. Quantification of the amino acid levels was performed by HPLC.Valproic acid (VPA) did not either induce changes on these neurotransmitters contents in corpus striatum after acute treatment. After chronic administration we found a decrease on the endogenous levels of glutamic acid (24%, p < 0.05) which was related to an increase (250%, p < 0.02) of the in vitro KCl evoked release of glutamate. We found decrements in taurine endogenous levels (22%, p < 0.05) which was not associated with an increase of its release.In cerebral frontal cortex there was not found any change neither under the acute nor under the chronic condition.Thus, it may be conclude that chronic treatment with VPA produces decreases on the endogenous levels of glutamate and taurine. However the relevance of this effect concerning it therapeutic action remains unclear.

摘要

研究了 200mg/kg(ip)丙戊酸(VPA)急性和慢性(10 天)给药对大鼠大脑前额叶皮层和纹状体中天冬氨酸、谷氨酸、丙氨酸、甘氨酸和牛磺酸内源性水平的影响。通过 HPLC 定量测定氨基酸水平。丙戊酸(VPA)在急性治疗后也没有引起纹状体中这些神经递质含量的变化。在慢性给药后,我们发现谷氨酸的内源性水平下降(24%,p < 0.05),这与谷氨酸体外 KCl 诱发释放的增加(250%,p < 0.02)有关。我们发现牛磺酸内源性水平下降(22%,p < 0.05),但与牛磺酸释放的增加无关。在大脑前额叶皮层中,无论是急性还是慢性条件下,都没有发现任何变化。因此,可以得出结论,慢性 VPA 治疗会导致谷氨酸和牛磺酸内源性水平降低。然而,这种作用与治疗作用的相关性尚不清楚。

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