Three experiments assessed the effects of β-amyloid 1-40 (βA4) on spatial learning in Sprague-Dawley rats. In Experiment 1, rats were trained on a signaled footshock avoidance in a Y-maze. Rats received a single injection of βA4 or vehicle in both sides of the hippocampus immediately after the fifth trial. The βA4 group took significantly longer than the vehicle group to learn to avoid the shock when trained to criterion 1 week later, suggesting a detrimental effect of βA4 on memory consolidation. Experiment 2 used a food reinforcer rather than shock relief under procedures similar to Experiment 1. Again, the βA4 group took longer to learn the maze to criterion. This shows that the effect in Experiment 1 was not specific to shock-maintained learning. In Experiment 3, rats were trained to retrieve a food pellet from each arm of an eight-arm radial maze. After training to criterion, β4 or vehicle was administered intrahippocampally 30 min before the daily session for 26 sessions. There were no acute or chronic effects of βA4 injection on radial maze performance, and no aggregation of βA4 or significant necrosis was observed upon postmortem histological analysis. These experiments suggest that single injections of βA4 impair memory consolidation, but repeated injections of βA4 over an extended period do not affect well-learned behavior.
Bibliographical noteFunding Information:
1 This work was supported by a Department of Veterans Affairs Merit Review grant awarded to J.C.M.M. was supported under NICHD Training Grant T32 HD07279 and completed this research in partial fulfillment of the degree of Doctor of Philosophy at the University of Minnesota. The authors thank Martha Grace for her expert technical assistance and Float Temi-yakarn for the excellent extramaze cues. The Institute for Disabilities Studies and the Center for Research in Learning, Perception, and Cognition, both of the University of Minnesota, also provided support for this study. Address reprint requests to James Cleary, GRECC, Minneapolis VAMC, 1 Veterans Drive, Minneapolis, MN 55417.