Alpha-phenyl-tert-butyl-nitrone (PBN) reverses age-related maze learning performance and motor activity deficits in C57 BL/6 mice

Abstract

Two experiments were performed to study the effects of age and repeated administration of alpha-phenyl-tert-butyl-nitrone (PBN), the free radical spin-trapping agent, upon spontaneous motor activity levels and radial arm maze performance in normal young (3 month old) and normal aged (15 month old) C57 BI/6 mice. In Experiment 1, the aged mice were found to show reduced locomotor and rearing behaviour in comparison with the young mice. In the radial eight-arm maze learning task, the aged mice performed at a comparable level to the young mice during the first learning trial (Day 1) but made significantly more errors and showed longer total latencies during the second trial presented 24h later. In Experiment 2, the aged and young mice were subchronically administered either PBN at a dose of 50mg/kg, s.c. over 12 days, or saline. Spontaneous motor activity was tested 72h after the last injection. 36h later the first test trial in the radial arm maze was presented; this was followed after a further 24h by the second test trial. Subchronic treatment with PBN increased locomotion counts in the aged (15 month old) mice during the 60min test period, but decreased rearing during the first 30min of the test period. In the radial arm maze, the performance deficit shown during the second test trial by the aged mice was abolished by repeated PBN administration; both the number of errors and the latencies to all eight pellets were significantly reduced in the aged mice that received PBN. PBN did not exert any effects upon the performance of the young mice. These results, considered in conjunction with other studies using gerbils or rats, implicate the involvement of free radical species in the deterioration of function in the aged C57 BI/6 mouse.