Dose-dependency of life span prolongation of F344/DuCrj rats injected with (-)deprenyl.
The effect of (-)deprenyl (D) on prolonging survival has previously been reported in different species of animals. In rats, three studies reported a positive effect, while one study reported a shortening of life spans. In the present study, we attempted to clarify past discrepancies in the results based on the speculation that there exists a certain effective dose range for this effect of the drug. F344/DuCrj rats of both sexes began to receive subcutaneous (s.c.) injections of D at the age of 18 months at a dose of 0.25 mg/kg/injection (inj.), 3 times a week. Control animals were given a vehicle (a saline solution). Average life spans of animals (days) were significantly increased in both male (895 +/- 109.7, n=30; 967.8 +/- 88.6, n=30, control vs. D treated, P<0.01, t-test) and female (924.7 +/- 132.2, n=38; 987.1 +/- 133.4, n=39, P<0.05) rats by 8.1% and 6.7%, respectively. We have previously reported that a dose of 0.5mg/kg/inj. (s.c.) significantly increased the life span of male F344 rats, while a dose of 1.0 mg/kg/inj. somewhat shortened the life span, although the difference was not statistically significant. The results of the present study coupled with our previous reports clearly indicate that a proper dose of D within a certain dose range can significantly increase the life span of animals of both sexes, but that a greater dose becomes less effective and may actually adversely affect the life span of rats. The presence of this effective dose range of D may explain discrepancies in the effect of D on life spans of animals previously reported.
Kitani
K
K
National Institute for Longevity Sciences, 36-3, Gengo, Moriokacho, Obu-shi, Tokyo, Japan. kitani@nils.go.jp
Kanai
S
S
Miyasaka
K
K
Carrillo
M C
MC
Ivy
G O
GO
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007279:Injections, Subcutaneous; D008136:Longevity / Q000187:drug effects*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012642:Selegiline / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline