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 relate d SAMR1/TaJf(R1) show no impairment. After training on footshock avoid ance, P8 and R1 received a drug injection into the hippocampus. Retent ion was tested 1 week later. The results indicate that bicuculline (GA BA antagonist), SKF38393 (DA agonist), and ST587 (NE agonist) facilita ted retention with little change in the dose-response curves for P8 mi ce 4, 8, and 12 months of age. L-glutamate, acting at the NMDA recepto r, showed a modest decline in ability to improve retention with increa sing age. Arecoline, a muscarinic agonist, had the strongest trend for an age-related decline in potency. The same drug treatments yielded d ose-dependent facilitation of retention but no age-related changes in R1 mice. Reduced cholinergic activity in the hippocampus may be, in pa rt, responsible for age-related decline in memory retention in P8 mice .