MPTP-Induced Parkinsonism in Minipigs

Fourteen male Göttingen minipigs were used in this study. Nine were administered N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dosage of 1 mg/kg/day, SC, for 6 days, the last five pigs received saline injections for 6 days. All MPTP-treated animals developed Parkinson symptoms, i.e., muscle rigidity, hypokinesia, and impaired coordination within 5 days. The brain levels of dopamine (DA), and its major metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were determined in caudatum and putamen 2, 14, and 93 days (n = 3/time point) after the last drug administration. In eight of the MPTP-treated animals, striatal DA, DOPAC, and HVA concentrations were reduced from 50 to 95% compared to control animals at all time intervals. Animals with the lowest striatal DA concentrations showed the most severe signs of Parkinsonism. The number of cells in substantia nigra (SN) showed a decline only 3 months after MPTP treatment. The minipigs represent a nonprimate model of MPTP-induced parkinsonism syndromes lasting at least months.