MPTP-induced parkinsonism in minipigs: A behavioral, biochemical, and histological study

Fourteen male Gottingen minipig were used in this study. Nine were administ ered N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dosage of 1 m g/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., muscl e rigidity, hypokinesia, and impaired coordination within 5 days. The brain levels of dopamine (DA), and its major metabolites dihydroxyphenylacetic a cid (DOPAC) and homovanillic acid (HVA), were determined in caudatum and pu tamen 2, 14, and 93 days (n = 3/time point) after the last drug administrat ion. In eight of the MPTP-treated animals, striatal DA, DOPAC, and HVA conc entrations were reduced from 50 to 95% compared to control animals at all t ime intervals. Animals with the lowest striatal DA concentrations showed th e most severe signs of Parkinsonism. The number of cells in substantia nigr a (SN) showed a decline only 3 months after MPTP treatment. The minipigs re present a nonprimate model of MPTP-induced parkinsonism syndromes lasting a t least months. (C) 1999 Elsevier Science Inc. All rights reserved.