Valproate Disturbs the Balance Between Branched and Aromatic Amino Acids in Rats

We investigated the effect of valproate (ip, 500 mg/kg), which is regarded as a potent plasma protein tryptophan (TRP) displacer, on the central nervous system (hippocampal) and peripheral (plasma) levels of the aromatic amino acids (AAAs; e.g. TRP, tyrosine and phenylalanine) and branched-chain amino acids (BCAAs; e.g. valine, isoleucine and leucine) as well as the other amino acids (glutamate, GABA, alanine, glutamine, glycine, aspartate and taurine) involved in the regulation of neurotransmission. Furthermore, we investigated whether the changes in the BCAA/AAA ratio affected the hippocampal concentration of monoamines [serotonin (5-HT), dopamine (DA) and noradrenaline (NA)]. Valproic acid (VPA) administration potently modified the balance between the BCAA and AAA. In the brain, the significantly increased AAA and decreased BCAA concentrations were followed by a decrease in the BCAA/AAA ratio. In the plasma, VPA significantly decreased the BCAA and AAA levels. The changes in the BCAA and AAA levels were accompanied by an increase in the NA, DA and 5-HT levels as well as hippocampal 5-HT metabolism. This novel finding indicates that VPA, through the displacement of TRP from its protein-binding sites, could disturb the BCAA/AAA ratio, with central nervous system consequences, including the possible contribution to VPAs effects in affective disorders.