The necessity of having a proper dose of (-)deprenyl (D) to prolong the life spans of rats explains discrepancies among different studies in the past.

(-)Deprenyl (D) has been shown to be effective in prolonging life span in experimental animals, although, there are some discrepancies in its effect on the life span the even within the same species (rats). The present study aims to clarify the reason for these discrepancies. Male F344/DuCrj rats began receiving subcutaneous (s.c.) injections of D at the age of 18 months. Doses used were 0.25, 0.50, and 1.0 mg/kg/injection (inj.), three times a week. Average life spans of animals were significantly longer in male rats given 0.25 and 0.5 mg/kg/inj.; however, rats given a 1.0 mg/kg dose began dying earlier than control rats, leading to an inverse U-shaped dose-efficacy relationship, a hormesis. Old (27-month-old) rats given different doses of D for 1 month showed a typical hormetic response for antioxidant enzyme activities, indicating a significant increase in superoxide dismutase (SOD) and catalase (CAT) activities in brain dopaminergic regions with four lower doses (0.25 to 2 mg/kg/inj., 3 times a week), but a significantly negative response with the highest dose (4 mg/kg/inj.). Our results clearly indicate that a proper dose of D within a certain dose range can significantly increase the life span of rats, but that a greater dose becomes less effective and may actually adversely affect the life span of rats. A similar hormetic response for its effect on antioxidant enzyme activities and the parallel between the two different effects of D suggest a possible causal relationship between these two effects of D. The presence of this effective dose range of D may explain previously reported discrepancies in the effect of D on the life span of animals.