SEVERE LONG-TERM METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE-INDUCED PARKINSONISM IN THE VERVET MONKEY (CERCOPITHECUS-AETHIOPS SABAEUS)

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) pro duces parkinsonian neurochemical and functional deficits in human and non-human primates. The utility of MPTP-induced parkinsonism in monkey s as an animal model of Parkinson's disease would be greater if it pro duced a persistent and stable behavioural syndrome so that the effects of novel therapeutic treatments can be accurately assessed. Further, the claim that many species including primates spontaneously recover f rom MPTP is a significant difference from idiopathic Parkinson's disea se. This experiment focused on the long-term (six months) persistence of behavioural deficits in severely and moderately parkinsonian monkey s. The severity of the syndrome was based on a quantitative and object ive measure of parkinsonism. Adult male African green (vervet) monkeys (Cercopithecus aethiops sabaeus) were treated with MPTP (cumulative d ose 2.5 mg/kg over five days), and six were saline-control treated. MP TP-treated subjects were examined in two groups: those that were sever ely parkinsonian (''severe'' group, n=11) and those that were moderate ly impaired (''moderate'' group, n=5) the month after treatment. Summa ry factor scores were examined reflecting abnormal (''parkinsonian'') behaviour and normal ''healthy'' behaviour. Subjects that displayed se vere parkinsonism the month after MPTP were found to show stable and s evere parkinsonism for the time period studied. In contrast, the group of animals that initially were moderately parkinsonian did not show a stable deficit during the study. These data suggest that the initial severity of the deficit is an important predictor of outcome. None the less, stable parkinsonism can be observed in severely parkinsonian su bjects despite variability in the severity of the impairment in respon se to MPTP treatment. Two moderately and three severely affected subje cts were studied for more than six months and they appeared to show eq uivalent scores at six months compared with between Il to 19 months af ter MPTP administration. MPTP-treatment in the vervet monkey can resul t in persistent long-term deficits and therefore provides an excellent phenomenological as well as neuropathological model of Parkinson's di sease. (C) 1997 IBRO. Published by Elsevier Science Ltd.