Summary
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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Bartnusz V, Aubry J-M, Pagliusi A, Jevoza D, Baffi J, Kiss JZ (1995) Stress-induced changes in messenger RNA levels of N-methy-D-aspartate and AMPA receptor subunits in selected regions of the rat hippocampus and hypothalamus. Neuroscience 66: 247–252
Biggs CS, Pearce BR, Fowler LJ, Whitton PS (1992) The effect of sodium valproate on extracellular GABA and other amino acids in the rat ventral hippocampus: an in vivo microdialysis study. Brain Res 594: 138–142
Chapman A, Keane PE, Meldrum BS, Simiand J, Vernieres JC (1982) Mechanisms of anticonvulsant action of valproate. Prog Neurobiol 19: 315–359
Dickinson DG, Harland RC, Ilias AM, Rodgers RM, Kaufman SN, Lynn RK, Gerber N (1979) Disposition of valproic acid in the rat: dose — dependent metabolism, distribution, enterohepatic recirculation and choleretic effect. J Pharmacol Exp Ther 211: 583–595
Durkin TA, Anderson GM, Cohen DJ (1988) HPLC analysis of neurotransmitter amino acid in brain. J Chromatogr 428: 9–11
Farrant M, Webster RA (1989) Neuronal activity, amino acid concentration and amino acid release in the substancia nigra of the rat after sodium valproate. Brain Res 504: 49–56
Fowler LJ, Beckford J, John RA (1975) An analysis of kinetics of inhibition of rabbit gamma aminobutyrate aminotransferase by sodium n-dipropylacetate and some other simple carboxylic acids. Biochem Pharmacol 24: 1267–1270
Glowinski J, Iversen LL (1966) Regional studies of catecholamines in rat brain. I. The disposition of3H-norepinefrine,3H-dopamine and3H-DOPA in various regions of the brain. J Neurochem 13: 665–669
Godin Y, Heiner L, Mark J, Mandel P (1969) Effect of di-n-propylacetate an anticonvulsive compound, on GABA metabolism. J Neurochem 16: 869–873
Harvey PKP, Bradford HF, Davidson AN (1975) The inhibitory effect of sodium ndipropylacetate on the degradative enzyme of the GABA shunt. FEBS Lett 52: 251–254
Hönack D, Rundfeldt C, Löscher W (1992) Pharmacokinetics, anticonvulsant efficacy and adverse effects of trans-2-en-valproate after acute and chronic administration in amygdala-kindled rats. Naunyn Schmiedebergs Arch Pharmacol 345: 187–196
Huxtable RJ (1989) Taurine in the central nervous system and the mammalian actions of taurine. Prog Neurobiology 32: 471–533
Hwa GG, Avoli M (1992) Excitatory synaptic transmission mediated by NMDA and non NMDA receptors in the superficial/middle layers of the epileptogenic human neocortex maintained in vitro. Neurosci Letters 143: 83–86
Kamphius W, Gorter JA, da Silva FL (1991) A long-lasting decrease in the inhibitory effect of GABA an glutamate responses of hippocampal pyramidal neurons induced by kindling epileptogenesis. Neuroscience 41: 425–431
Kontro P, Oja S (1987) Taurine and GABA release from mouse cerebral cortex slices: effects of structural analogues and drugs. Neurochemical Res 12: 475–485
Lehmann A, Sandberg M, Huxtable RJ (1986) In vivo release of neuroactive amines and amino acids from the hippocampus of seizure-resistant and seizure-susceptible rats. Neurochem Int 8: 513–520
Löscher W (1980) Comparative study of the inhibition of GABA aminotransferase by different anticonvulsant drugs. Arch Int Pharmacodyn Ther 243: 48–55
Löscher W (1981) Effect of inhibitors of GABA aminotransferase on the metabolism of GABA in brain tissue and synaptosomal fractions. J Neurochem 36: 1521–1527
Martin-Gallardo A, Rodriguez P, López M, Benavides J, Ugarte M (1985) Effects of dipropylacetate on the glycine cleavage enzyme system and glycine levels. A possible experimental approach to non-ketotic hyperglycinemia. Biochem Pharm 34: 2877–2882
Masukawa LM, Higashima M, Hart GJ, Spencer DD, O'Connor MJ (1991) NMDA receptor activation during epileptiforme responses in the dentate gyrus of epileptic patients. Brain Res 562: 176–180
McCabe RT, Wasterlain CG, Kucharczyk R, Duane Sofia R, Vogel JR (1992) Evidence for anticonvulsant and neuroprotectant action of felbamate mediated by strychnineinsensitive glycine receptors. J Pharmac Exp Ther 264: 1248–1252
McNamara JO, Russell RD, Rigsbee L, Bonhaus DW (1988) Anticonvulsant and antiepileptogenic actions of MK-801 in the kindling and electroshock models. Neuropharmacology 27: 563–568
Oja SS, Kontro P (1987) Cattion effects on taurine release from brain slices: comparation to GABA. J Neurosci Res 17: 302–311
Palkovits M, Lang T, Patthy A, Elekes I (1986) Distribution and stress-induced increase of glutamate and aspartate levels in discrete brain nuclei of rats. Brain Res 373: 252–257
Patsalos PN, Lascelles PT (1981) Changes in regional brain levels of amino acid putative neurotransmitters after prolonged treatment with the anticonvulsant drugs diphenylhydantoin, phenobarbitone, sodium valproate, ethosucimide, and sulthiamine in the rat. J Neurochem 36: 688–695
Philibert RA, Rogers KL, Allen AJ, Dutton GR (1988) Dose-dependent K+-stimulated efflux of endogenous taurine from primary astrocyte cultures is Ca2+ dependent. J Neurochem 51: 122–126
Schechter PJ, Tranier Y, Grove J (1978) Effect on n. dipropylacetate on amino acid concentrations in mouse brain: correlations with anti-convulsant activity. J Neurochem 31: 1325–1327
Simila S, von Wendt L, Lima SL, Saukkonen AL, Huhtaniemi I (1979) Dipropylacetate and hyperglycinemia. Neuropaediatrie 1: 158–160
Van der Laan JW, de Boer T, Bruinvels J (1979) Di-n-propylacetate and GABA degradation. Preferential inhibition of succinic semialdehyde dehydrogenase and indirect inhibition of GABA transaminase. J Neurochem 32: 1769–1780
Vezzani A, Wu H-Q, Moneta E, Samanin R (1988) Role of the N-methyl-D-aspartatetype receptors in the development and maintenance of hippocampal kindling in rats. Neurosci Lett 87: 307–322
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Acosta, G.B., Wikinski, S.I., Bonelli, C.C.G. et al. Chronic administration of valproic acid induces a decrease in rat striatal glutamate and taurine levels. Amino Acids 10, 123–131 (1996). https://doi.org/10.1007/BF00806585
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00806585