Neurotoxic effects of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the cat. Tyrosine hydroxylase immunohistochemistry.

N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces substantia nigra pars compacta (SNc) cell death in several species including the mouse, dog and monkey. MPTP is presently shown to cause apparent nigral cell death in the SNc of the cat as noted by a long-lasting decrease in tyrosine-hydroxylase (TH)-like cell staining. A transient loss of TH-like staining is also observed in the ventral tegmental area, locus coeruleus and retrorubral area. These latter areas appear normal 1.5-5.0 months after MPTP administration. The caudate nucleus (CD) showed a greater TH depletion than the nucleus accumbens (ACC) and only recovered slightly over time. After 7 days of MPTP, an apparent axonopathy, characterized by lightly staining fibers with large TH-positive varicosities, is seen in the CD and to a lesser extent, in the ACC. These findings demonstrate that MPTP is toxic to the cat's nigrostriatal dopaminergic system and suggests that the cat is a good intermediate species in which to study the responses of dopaminergic neurons to MPTP.