Effects of valproate on amino acid and monoamine concentrations in striatum of audiogenic seizure-prone balb/c mice |
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Authors: | Jerry P Vriend and Nancy A M Alexiuk |
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Institution: | (1) Department of Anatomy, University of Manitoba, R3E 0W3 Winnipeg, MB, Canada |
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Abstract: | The effects of aalproate on CNS concentrations of γ-aminobutyric acid (GABA), glutamate (GLU), glutamine (GLN), dopamine (DA),
serotonin (5-HT), and metabolites were examined in tissue extracts of caudate nucleus of genetic substrains of Balb/c mice
susceptible (EP) or resistant (ER) to audiogenic seizures. Generalized tonic-clonic seizures observed in EP mice were inhibited
by valproate, administered 1 h prior to testing, in a dose-response fashion. Concentrations of GABA, GLU, and GLN, which were
lower in EP mice than in ER mice, were significantly increased by valproate at doses of 180 and 360 mg/kg. Concentrations
of homovanillic acid (HVA) and hydroxyindoleacetic acid (5-HIAA), metabolites of DA and 5-HT were substantially increased
by valproate at these doses. Thein situ activity of tyrosine hydroxylase (TH) was not significantly influenced by valproate, whereas a valproate-induced increase
in tryptophan hydroxylase (TPH) activity was observed in both striatum and in midbrain tegmentum. The data are consistent
with the interpretation that anticonvulsive doses of valproate influences the intraneuronal metabolism of monoamines, GABA,
and glutamate concurrently. Valproate’s influence on the metabolism of both major inhibitory (GABA) and excitatory (GLU) amino
acids in striatum could contribute to its anticonvulsive effects in genetically seizure-prone mice, as well as to the accumulation
of DA and 5-HT metabolites. |
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Keywords: | Valproate GABA glutamate dopamine serotonin seizures striatum caudate nucleus |
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