REGIONAL ALTERATIONS OF DOPAMINE AND ITS METABOLITES IN RAT-BRAIN FOLLOWING PORTACAVAL ANASTOMOSIS

Hyperammonemia and changes in brain monoamine metabolism have been pro posed to contribute to the pathogenesis of the neuropsychiatric sympto ms characteristic of human portal-systemic encephalopathy (PSE) result ing from chronic liver disease. Portacaval anastomosis (PCA) in the ra t leads to sustained hyperammonemia and mild encephalopathy. In order to evaluate the role of dopamine (DA) metabolism in PSE, levels of DA and its metabolites were measured by HPLC with electrochemical detecti on in brain regions of rats with PCA at various stages of encephalopat hy precipitated by ammonium acetate administration. Following ammonium acetate administration, rats with PCA rapidly develop severe neurolog ical signs of encephalopathy progressing through loss of righting refl ex to coma; sham-operated control animals administered ammonium acetat e showed no such neurological deterioration. Concentrations of the DA metabolites DOPAC and HVA as well as [DA metabolites]/[DA] ratios, an indirect measure of DA turnover in brain, were increased in caudate-pu tamen, in cingulate and pyriform entorhinal cortices as well as in rap he nucleus and locus coeruleus. Increased DA metabolites, however, did not worsen at coma stages of PSE. Increased DA turnover thus appears to relate to early neuropsychiatric and extrapyramidal symptoms of PSE .