NITRIC-OXIDE SYNTHASE INHIBITION AND MPTP-INDUCED TOXICITY IN THE COMMON MARMOSET

Nitric oxide, produced following activation of N-methyl-D-aspartate (N MDA) receptors, may be involved in 1-methyl-4-phenyl-1,2,3,6-tetrahydr opyridine (MPTP) toxicity since NMDA receptor antagonists have been sh own to prevent MPTP induced nigral cell loss in primates. Common marmo sets were treated with either saline or MPTP or L-N(G)nitro arginine m ethyl ester (L-NAME) or MPTP and L-NAME. MPTP-treated common marmosets showed motor deficits including bradykinesia, rigidity and tremor acc ompanied by a marked lass of tyrosine hydroxyl ase-immunoreactive neur ones in the substantia nigra pars compacta and of [H-3]-mazindol bindi ng in the caudate-putamen. MPTP treatment also caused an increase in g lial fibrillary acidic protein (GFAP) staining in the substantia nigra compared to controls. However, MPTP treatment did not alter the numbe r of constitutive nitric oxide synthase-immunoreactive neurones in the caudate-putamen, Furthermore, neurones or glial cells immunoreactive for inducible nitric oxide synthase were not observed in the substanti a nigra pars compacta following MPTP treatment. L-NAME treatment alone did not produce any behavioural changes in marmosets and did not alte r the number of tyrosine hydroxylase-immunoreactive cells in the subst antia nigra pars compacta, the number of constitutive nitric oxide syn thase-immunoreactive neurones or [H-3]-mazindol binding in the caudate -putamen compared to saline-treated control animals. Furthermore, L-NA ME did not affect the motor deficits, loss of tyrosine hydroxylase-imm unoreactive neurones in the substantia nigra pars compacta, loss of [H -3]-mazindol binding in the caudate-putamen, or the increase in GFAP s taining in the substantia nigra induced by MPTP treatment of common ma rmosets. The failure of L-NAME to protect against MPTP-induced toxicit y in the marmoset suggests that nitric oxide does not play a major rol e in such toxicity and casts doubt over the involvement of the NMDA:ni tric oxide system in neurodegeneration in MPTP-treated primates. (C) 1 997 Wiley-Liss, Inc.