COMPARISON OF BRAIN DOPAMINE DEPLETION INDUCED BY LOW-DOSE 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP) IN YOUNG AND AGED

Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on dopa mine levels in the striatum (ST), substantia nigra (SN), olfactory tub ercle (OT), ventral tegmental area (VTA) and nucleus accumbens (NA) we re 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. dai ly for 8 days) both young and old rats showed a marked depletion of do pamine (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-t reated rats than those in old controls. The concentrations of DA, DOPA C and HVA remained unchanged in the SN and VTA of both young and old r ats after MPTP treatment. These results indicate that multiple treatme nt of low-dose MPTP selectively causes more widespread damage to dopam inergic neurons in old rats than in young ones, and further support th e view that effects of MPTP on the dopaminergic system in rats may dep end on age.