THE OPTIMAL DOSAGE OF (-)DEPRENYL FOR INCREASING SUPEROXIDE-DISMUTASE ACTIVITIES IN SEVERAL BRAIN-REGIONS DECREASES WITH AGE IN MALE FISCHER 344 RATS

We previously reported that the optimal dosage of (-)deprenyl to increase superoxide dismutase (SOD) activities in striatum in rats differs 10 fold between young male and female rats (1). Furthermore, in female rats the optimal dosage increased with age (1). In the present study in order to clarify how the optimal dosage of this effect changes with age in male rats, we examined the effects of four different dosages of deprenyl on SOD enzyme activities in striatum and several other tissues in old (28-29-month-old) male Fischer 344 (F-344) rats. Continuous s.c. infusion of deprenyl for 3 wks increased activities of SOD and catalase (CAT) in striatum, substantia nigra and cortical regions but not in hippocampus, cerebellum or the liver. The dose of 0.5 mg/kg/day was found to be most effective, while higher (1.0, 2.0 mg/kg/day) or lower (0.1 mg/kg/day) dosages were less effective. This value of 0.5 mg/kg/day was 4 fold lower than the dosage of 2.0 mg/kg/day which was most effective in increasing SOD and CAT activities in young (5-7 month old) male rats of the same strain (1,2). The decline of the optimal dosage with age found in male rats is best explained by a possible decline with age in the hepatic microsomal monooxygenase enzyme activities that are involved with the metabolism of deprenyl. In view of the large differences in the optimal dosages shown among different sexes and ages of rats, future studies regarding the unique effect of this drug in prolonging the life span of rats must be carefully investigated with the caution in mind that the optimal dosage for the life prolonging effect may well differ depending on sex, age and possibly strain and species of animal model used.