Repeated administration of N-methyl-4-phenyl 1,2,5,6-tetrahydropyridine to rats is not toxic to striatal dopamine neurones.

N-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine ( MPTP ) (10 mg/kg/day i.p.) was administered to rats for 16 days, which were then observed for a further 9-11 days. MPTP administration did not alter spontaneous locomotor activity or amphetamine (2.5 mg/kg ip)-induced locomotion. Apomorphine (0.25 mg/kg sc) did not alter locomotion in control rats but increased activity in MPTP treated animals. The stereotyped response to apomorphine (0.25 mg/kg sc) and amphetamine (2.5 and 5.0 mg/kg ip) was unaltered by MPTP administration. The striatal content of dopamine, HVA and DOPAC was unaltered by MPTP intake. The uptake of [3H]dopamine and [3H] 5HT in striatal synpatosomes was not changed by MPTP . The results suggest that MPTP , in the dose used, is not toxic to nigro-striatal dopamine neurones in the rat. This contrasts with its neurotoxic actions in monkeys and man.