EFFECT OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE IN GOLDFISH CEREBELLUM - NEUROCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administered in go ldfish for 3 consecutive days (10 mg kg(-)1 i.p.), caused cerebellar d isappearance of dopamine-hydroxylase (DBH) immunoreactive fibres, wher eas the noradrenergic cell bodies located in the medulla oblongata app eared intact. This effect was coupled with marked decreases in cerebel lar noradrenaline (NA) and dopamine (DA) levels. An increase of immuno staining for glial fibrillary acidic protein (GFAP) was also observed. In the cerebellum of MPTP-treated fish, the contents of glutamate and GABA were significantly reduced, whereas glutamine was strongly incre ased. These modifications were concomitant with a significant increase of glutamine synthetase (GS) activity, whereas glutamic acid decarbox ylase (GAD) activity was decreased. No changes in choline acetyltransf erase (ChAT) and ornithine decarboxylase (ODC) activities were observe d. High affinity uptake of glutamate and GABA was strongly reduced. Pr etreatment of fish with either the monoamine oxidase inhibitor pargyli ne or the catecholamine (CA) uptake blocker mazindol largely prevented such modifications. The NMDA-sensitive glutamate receptor uncompetiti ve antagonist, dizocilpine maleate (MK-801), failed to protect against MPTP-induced damage. In conclusion, the neurotoxic effects of MPTP in goldfish cerebellum appear to be not specific against catecholaminerg ic terminals and could promote astrocytic reactions. (C) 1998 Elsevier Science B.V.