Long term treatment with (-)deprenyl reduces the optimal dose as well as the effective dose range for increasing antioxidant enzyme activities in old mouse brain

C57BL mice of the male sex received different doses of (-)deprenyl (0.25, 0.5, 1.0 mg/kg per injection 3 times a week, s.c.) for 3 months beginning at the age of 26 months. At the age of 29 months, animals were sacrificed and superoxide dismutase (SOD) and catalase (CAT) activities were examined in several brain regions. The dose of 0.5 mg/kg (3 times a week) was most effective in increasing SOD and CAT activities in S. nigra, striatum and cerebral cortex but not in hippocampus or cerebellum. The dose of 0.25 mg/kg was also effective in increasing enzyme activities, but the effect was much lower than the dose of 0.5 mg/kg. The magnitudes of increase in enzyme activities with the dose of 0.5 mg/kg, however, were generally much lower than respective values we previously found in animals treated with (-)deprenyl for only 3 weeks. The highest dose of 1.0 mg/kg had negligible effect. Enzyme activities in all groups of animals that were examined 2 weeks after the last (-)deprenyl dose were practically the same as respective control values. Together with the results from our previous study with short term (-)deprenyl treatment in old mice, these results replicate our previous findings in old female rats. We showed that longer term treatment with (-)deprenyl reduces the optimal dose for increasing antioxidant enzyme activities by a factor of 5 to 10. The present study further indicates that longer term treatment with (-)deprenyl also reduces the effective dose range of (-)deprenyl as well as the magnitude of increase of enzyme activities. If the effect of (-)deprenyl for increasing these antioxidant enzyme activities in selective brain regions is causally related to its effect of increasing average life expectancies of animals, the selection of a proper dose of the drug may be a critical factor for life span studies in which the drug is administered for more than one year.