MPTP-induced behavioural and biochemical deficits: a parametric analysis.

Two experiments were performed to study the parametric effects of long-term administration of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), as a functional model of parkinsonism in mice. The behavioural deficits induced by different doses of MPTP (5, 10, 20, 30 or 40 mg/kg, s.c., each injected on two occasions) at a 3-week or a 3-month treatment-testing interval were evidenced by significant reductions of spontaneous motor activity, from the 10 mg/kg dosages upwards at the 3-week interval and from 30-40 mg/kg at the 3-month interval. Significant dopamine (DA) reductions in the mouse striatum were obtained at these dose levels and intervals. The behavioural deficit of the 40 mg/kg dose (injected on two occasions) and tested at the 3-, 6-, 12-, 24- and 40-week intervals (separate as well as repeated testing groups) indicated marked and relatively comparable reductions of all three parameters of motor activity, locomotion, rearing and total activity. DA depletions were severe at all five test intervals. These results offer functional and neurochemical evidence that MPTP treatment produces permanent damage to the nigrostriatal motor system in mice.