Dietary restriction does not protect the nigrostriatal dopaminergic pathway of older animals from low-dose MPTP-induced neurotoxicity

To determine whether reduced caloric intake affects the susceptibility of nigrostriatal dopamine (DA) neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity, 1-year-old male C57BL6 mice were offered food ad libitum or were given only 60% of the normal dietary intake. After 3 months, both groups were treated with low cumulative doses of 0, 10, 15, or 20 mg/kg MPTP. One week later, the striata were collected and DA, dihydroxyphenylalanine (DOPAC), and norepinephrine (NE) were measured. Treatment with MPTP had no effect on striatal NE but produced a dose-related depletion of DA and DOPAC in both the ad libitum-fed and the dietary-restricted mice. The MPTP-induced depletions of DA and DOPAC were not ameliorated in the dietary-restricted versus the ad libitum-fed mice. Baseline DA levels and those observed after treatment with the 15-mg/kg dose of MPTP were lower in the dietary-restricted mice compared with the ad libitum-fed mice. Overall, these results suggest that, at least in 1-year-old mice, dietary restriction for 3 months does not protect nigral DA nerve terminals from low toxic dosages of MPTP.