Chronic valproic acid therapy and synaptic markers of amino acid neurotransmission.

Valproic acid acutely alters regional brain concentrations of GABA and of aspartic and glutamic acids in vivo, and it potentiates the action of these amino acid neurotransmitters on neurons in vitro. Chronic alterations of presynaptic uptake or receptor binding activity induced by these effects of valproate could contribute to its anticonvulsant properties. We treated rats with valproate (100 mg/kg ip bid) for 3 weeks; drug levels in frontal cortex reached 70 micrograms/g tissue, but there was no effect on uptake and binding activity of these amino acids in cortex and hippocampus.