PARKINSON-LIKE DISEASE BY 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP) TOXICITY IN MACACA-FASCICULARIS - SYNAPTOSOMAL METABOLISM ANDACTION OF DIHYDROERGOCRIPTINE

The maximal rates (V-max) of some enzyme activities related to synapto somal energy metabolism were studied in different types of synaptosome s from cerebellar cortex of Macaca Fascicularis (Cynomolgus monkey). D ifferent synaptosomal populations, namely ''large'' and ''small'' syna ptosomes, were isolated from the anterior lobule of the cerebellar cor tex of monkeys treated p.o. with dihydroergocriptine at the dose of 12 mg/kg/day before and during the induction of a Parkinson's-like syndr ome by MPTP administration (i.v., 0.3 mg/kg/day for 5 days). The enzym es were chosen according to their regulatory role and as markers of th e following metabolic pathways: (a) glycolysis ((hexokinase, phosphofr uctokinase, lactate dehydrogenase), (b) Krebs' (TCA) cycle (citrate sy nthase, malate dehydrogenase), (c) amino acid, glutamate metabolism (g lutamate dehydrogenase, glutamate-pyruvate- and glutamate-oxaloacetate -transaminases), (d) acetylcholine catabolism (acetylcholinesterase) a nd (e) ATPases, i.e. Na+-K+-ATPase, Mg2+-ATP synthetase, Mg2+-ATPase, Ca2+-Mg2+-ATPase and Ca2+-ATPase Low and High affinity for Ca2+. The M PTP administration modified the activities of citrate synthase, malate dehydrogenase, Na+-K+-ATPase, acetylcholinesterase and glutamate-oxal oacetate transaminase only on selected types of synaptosomes. Pharmaco logical treatment by dihydroergocriptine was able to recovery at the s teady-state levels the activities of these enzymes, thus demonstrating a partial protective effect on these biochemical parameters.