Comparison of brain dopamine depletion induced by low-dose 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in young and aged rats.

Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on dopamine levels in the striatum (ST), substantia nigra (SN), olfactory tubercle (OT), ventral tegmental area (VTA) and nucleus accumbens (NA) were studied in young (1 month) and old (21 months) male Long-Evans rats. Following repeated treatment with MPTP at low dose (3 mg/kg i.p. daily for 8 days) both young and old rats showed a marked depletion of dopamine (DA) concentrations in the ST compared to those of age-matched saline-treated controls. However, a significant reduction in DA levels was observed in the OT and NA of old but not young rats treated with MPTP. In contrast, no changes in 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in these three regions were seen in either young or old MPTP-treated rats. However, the ratio of DOPAC/DA and HVA/DA in the ST and NA were significantly higher in old MPTP-treated rats than those in old controls. The concentrations of DA, DOPAC and HVA remained unchanged in the SN and VTA of both young and old rats after MPTP treatment. These results indicate that multiple treatment of low-dose MPTP selectively causes more widespread damage to dopaminergic neurons in old rats than in young ones, and further support the view that effects of MPTP on the dopaminergic system in rats may depend on age.