Evidence for a serotonin transporter deficit in experimental acute liver failure

It has been suggested that alterations of serotonin transport may be implic ated in the pathogenesis of the neuropsychiatric symptoms encountered in ac ute liver failure. In order to address this issue, microdialysate concentra tions of serotonin, its precursor L-tryptophan and metabolite 5-hydroxyindo leacetic acid (5-HIAA) as well as brain regional distribution of serotonin transporter ([(3H)]-citalopram) sites were measured in rats with acute live r failure resulting from hepatic devascularization. A significant loss of [ H-3]-citalopram sites was observed in dorsal Raphe nucleus, in frontal and frontoparietal cortices as well as in substantia nigra of rats with severe encephalopathy resulting from acute liver failure. In frontal cortex, this loss of transporter binding sites was accompanied by significant increases of L-tryptophan, serotonin and 5-HIAA concentrations in extracellular fluid . Pharmacological manipulation of the brain serotonin system could afford a novel therapeutic approach to the prevention of the neuropsychiatric sympt oms characteristic of acute liver failure in humans. (C) 2001 Elsevier Scie nce Ltd. All rights reserved.