Effect of probenecid on 5-hydroxyindoleacetic acid in cisternal cerebrospinal fluid of rats with portacaval anastomosis

Portal-systemic encephalopathy (PSE) is characterized by a neuropsychiatric disorder progressing through personality changes, to stupor and coma. Previous studies have revealed alterations of serotonin and of its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in brain tissue and CSF in experimental (rat) and human PSE. Increased brain 5-HIAA concentrations could result from its decreased removal rather than to increased serotonin metabolism. In order to evaluate this possibility, CSF 5-HIAA concentrations were measured using an indwelling cisterna magna catheter technique at various times following end-to-side portacaval anastomosis in rats (the most widely used animal model of PSE) treated with probenecid, a competitive inhibitor that blocks the active transport of acid metabolites out of the brain and CSF. Following portacaval anastomosis and probenecid treatment, CSF concentrations of 5-HIAA were increased to a greater extent than in sham-operated controls. When data were expressed as per-cent baseline values, the relative increase of CSF 5-HIAA in portacaval shunted rats following probenecid treatment was not significantly different from sham-operated controls. These findings confirm that increased 5-HIAA in the CNS in experimental PSE results from increased 5HT metabolism or turnover and that the probenecid-sensitive acid metabolite carrier is intact in PSE.