NO CHANGE OF BRAIN EXTRACELLULAR CATECHOLAMINE LEVELS AFTER ACUTE CATECHOL-O-METHYLTRANSFERASE INHIBITION - A MICRODIALYSIS STUDY IN ANESTHETIZED RATS

Catechol-O-methyltransferase inhibitors have been newly introduced as adjunct drugs to the levodopa/dopa decarboxylase inhibitor therapy in Parkinson's disease. When given alone, catechol-O-methyltransferase in hibitors seem to affect behaviour. We wanted to determine whether the concentrations of free amine would be increased by catechol-O-methyltr ansferase inhibition with tolcapone and underpin the positive behaviou ral effects. To this end, dopamine and noradrenaline levels were analy zed in the microdialysis perfusion fluid collected from several brain regions in chloral hydrate anaesthetized rats. We also analyzed the tu rnover rate of catecholamines in the brain after single doses of tolca pone and entacapone using the alpha-methyl-p-tyrosine method. On their own, tolcapone (at 10 or 30 mg/kg) did not elevate dopamine or noradr enaline levels in any brain region studied although the formation of c atechol-O-methyltransferase-dependent metabolites was strongly reduced . Neither tolcapone nor entacapone (at 30 mg/kg) affected the turnover rate of catecholamines. It seems that catechol-O-methyltransferase in hibitors do not alter behaviour by elevating extracellular levels of f ree catecholamines levels but other explanations are needed. (C) 1998 Elsevier Science B.V. All rights reserved.