Ikonen_1999_Eur.J.Pharmacol_372_117

In the near future, a number of transgenic mouse models with neuropathological characteristics of Alzheimer's disease are expected to become widely available. 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 behavioral tests, i.e., water maze spatial navigation, Y-maze and passive avoidance behavior. These experiments were complemented by an investigation of the effects of acute treatment with an acetylcholinesterase inhibitor, metrifonate, in these behavioral tests. Normal C75BL mice perform very well in the water maze and the Y-maze, but suboptimally in the passive avoidance task. Lesioning of the medial septum or the dorsal hippocampus clearly impaired the performance of the mice. In medial septal-lesioned mice, metrifonate stimulated spatial navigation and alleviated the loss of activity in the Y-maze and passive avoidance. In hippocampal-lesioned mice, metrifonate had no effect on spatial navigation. It is concluded that C75BL mice are useful for testing in classical models for learning and memory, and that septohippocampal pathology is very likely to induce cognitive deficits in some of these models.