Objective:To observe the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the spatial learning ability/memory and dopaminergic neurons in the Nigra of senescence accelerated-prone 8 (SAMP8) mice.Methods: Three-month old male SAMP8 mice were injected with MPTP (36 mg/kg,s.c.) for 5 days,and animals in the control group were injected with NS (36 ml/kg,s.c.) in the same manner.Morris water maze was used to examine the searching strategy,seeking-platform latency,and the swimming time in the aimed quadrant.Immunohistochernistry was used to observe the changes of TH-ir positive neurons in substantia nigra.Results: The number of TH-ir neurons in substantia nigra pars compacta was significantly reduced in MPTP group compared with the control group(P<0.01).Morris water maze showed that the searching strategy of animals in MPTP group was worse than in the control group,with the seeking-platform latency of MPTP mice significantly prolonged (P<0.01),the time spent in the aimed quadrant significantly decreased (P<0.01) and time in the opposite quadrant significantly prolonged (P<0.05).Conclusion: MPTP can cause damage to the dopaminergic neurons in the substantia nigra of SAMP8 mice,which is subsequently followed by deficit in the spatial learning and memory in the animals.