EFFECT OF PROBENECID ON 5-HYDROXYINDOLEACETIC ACID IN CISTERNAL CEREBROSPINAL-FLUID OF RATS WITH PORTACAVAL ANASTOMOSIS

Portal-systemic encephalopathy (PSE) is characterized by a neuropsychi atric disorder progressing through personality changes, to stupor and coma. Previous studies have revealed alterations of serotonin and of i ts metabolite 5-hydroxyindoleacetic acid (5-HIAA) in brain tissue and CSF in experimental (rat) and human PSE. Increased brain 5-HIAA concen trations could result from its decreased removal rather than to increa sed 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 a nastomosis in rats (the most widely used animal model of PSE) treated with probenecid, a competitive inhibitor that blocks the active transp ort of acid metabolites out of the brain and CSF. Following portacaval anastomosis and probenecid treatment, CSF concentrations of 5-HIAA we re 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 treatme nt 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 probene cid-sensitive acid metabolite carrier is intact in PSE.