Age-related changes in hippocampal drug facilitation of memory processing in SAMP8 mice.

SAMP8/TaJf(P8) mouse strain has an inherited age-related impairment of learning and memory, while age-matched subjects of the closely related SAMR1/TaJf(R1) show no impairment. After training on footshock avoidance, P8 and R1 received a drug injection into the hippocampus. Retention was tested 1 week later. The results indicate that bicuculline (GABA antagonist), SKF38393 (DA agonist), and ST587 (NE agonist) facilitated retention with little change in the dose-response curves for P8 mice 4, 8, and 12 months of age. L-glutamate, acting at the NMDA receptor, showed a modest decline in ability to improve retention with increasing age. Arecoline, a muscarinic agonist, had the strongest trend for an age-related decline in potency. The same drug treatments yielded dose-dependent facilitation of retention but no age-related changes in R1 mice. Reduced cholinergic activity in the hippocampus may be, in part, responsible for age-related decline in memory retention in P8 mice.