The effect of valproic acid on the 5-hydroxyindoleacetic, homovanillic and lactic acid levels of cerebrospinal fluid.

In this study the cisternal cerebrospinal fluid (CSF) contents of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were sequentially measured in free-moving rats which were administered 50-500 mg X kg-1 valproic acid. Animals receiving 100-500 mg X kg-1 valproic acid showed significant increases in CSF 5-HIAA and HVA content, with maximal accumulation rates of 1.80-2.10 and 0.25-0.30 nmol X ml-1 X h-1, respectively, being reached at the 250-mg X kg-1 dose. The combination of valproic acid 500 mg X kg-1 and probenecid 300 mg X kg-1 failed to increase the accumulation rates of 5-HIAA and HVA over those seen with valproic acid 500 mg X kg-1 or probenecid 300 mg X kg-1 alone. This pattern of change indicates that valproic acid and probenecid share a common site of action in blocking the clearance of 5-HIAA and HVA from CSF. The tranquillizer diazepam produced progressive increases in CSF 5-HIAA and HVA content which suggested a similar action to that of valproic acid and probenecid. The anticonvulsants phenytoin and phenobarbital produced selective increases in 5-HIAA, whereas the tranquillizer chlorpromazine produced proportionally larger increases in HVA, changes which seem to indicate a more selective effect of these drugs on the serotonergic or dopaminergic systems, respectively. Valproic acid was associated with increases in CSF lactate which occurred in the absence of similar increases of blood or tissue lactate. This indicated that valproic acid, like probenecid, can inhibit the monocarboxylic acid transport system which removes lactate from the CSF.