Characterization of learning and memory behaviors and the effects of metrifonate in the C57BL strain of mice

In the near future, a number of transgenic mouse models with neuropathologi cal characteristics of Alzheimer's disease are expected to become widely av ailable. It will be important to characterize their behavior in models for learning and memory. As a first step, we have characterized normal, medial septal-lesioned and hippocampal-lesioned C57BL mice, in different behaviora l tests, i.e., water maze spatial navigation, Y-maze and passive avoidance behavior. These experiments were complemented by an investigation of the ef fects of acute treatment with an acetylcholinesterase inhibitor, metrifonat e, in these behavioral tests. Normal C75BL mice perform very well in the wa ter maze and the Y-maze, but suboptimally in the passive avoidance task. Le sioning of the medial septum or the dorsal hippocampus clearly impaired the performance of the mice. In medial septal-lesioned mice, metrifonate stimu lated spatial navigation and alleviated the loss of activity in the Y-maze and passive avoidance. In hippocampal-lesioned mice, metrifonate had no eff ect on spatial navigation. It is concluded that C75BL mice are useful for t esting in classical models for learning and memory, and that septohippocamp al pathology is very likely to induce cognitive deficits in some of these m odels. (C) 1999 Elsevier Science B.V. All rights reserved.