Further evidence for a dissociation between different forms of mnemonic expressions in a mouse model of age-related cognitive decline: Effects of tacrine and S 17092, a novel prolyl endopeptidase inhibitor

It has been demonstrated previously on the radial maze that the emergence o f an age-related mnemonic impairment is critically dependent on the form wh ich the discrimination problems took. Hence, when the arms were presented o ne by one (i.e., successive go-no-go discrimination), both adult and aged m ice learned to distinguish between positive (baited) and negative (unbaited ) arms readily, as evidenced by their increased readiness to enter positive relative to negative arms (i.e., by a differential in arm-entry latencies) . A selective impairment in the aged mice was seen when these arms were pre sented subsequently as pairs, such that the mice were confronted with an ex plicit choice (i.e., simultaneous 2-choice discrimination). When discrimina tive performance was measured by the differential run speed between positiv e and negative arms, aged mice were also impaired. This was particularly pr onounced in the 2-choice discrimination condition. We examined the effects of tacrine (3mg/kg, subcutaneously) or S 17092 (10mg/kg, orally) in aged mi ce on the three behavioral indices of this 2-stage spatial discrimination p aradigm. The results indicated that: (1) Tacrine, but not S 17092, enhanced the acquisition of go-no-go discrimination as reflected in arm-entry laten cies; (2) both drugs improved choice accuracy in simultaneous discriminatio n, although the effect of tacrine was less striking and, in particular, far from statistical significance in the very first 2-choice responses; and (3 ) neither drugs significantly affected run-speed performance. We conclude f urther that the specific patterns of drug effects on the three indices of d iscriminative performance might suggest that each index is associated with a distinct form of mnemonic expression relying on separate neural systems.