EFFECTS OF AN EXOGENOUS BETA-AMYLOID PEPTIDE ON RETENTION FOR SPATIAL-LEARNING

Three experiments assessed the effects of beta-amyloid 1-40 (beta A4) 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 beta A4 or vehicle in both sides of the hippocam pus immediately after the fifth trial. The beta A4 group took signific antly longer than the vehicle group to learn to avoid the shock when t rained to criterion I week later, suggesting a detrimental effect of b eta A4 on memory consolidation. Experiment 2 used a food reinforcer ra ther than shock relief under procedures similar to Experiment 1. Again , the beta A4 group took longer to learn the maze to criterion. This s hows that the effect in Experiment 1 was not specific to shock-maintai ned learning. In Experiment 3, rats were trained to retrieve a food pe llet fi om each arm of an eight-arm radial maze. After training to cri terion, beta A4 or vehicle was administered intrahippocampally 30 min before the daily session for 26 sessions. There were no acute or chron ic effects of beta A4 injection on radial maze performance, and no agg regation of beta A4 or significant necrosis was observed upon postmort em histological analysis. These experiments suggest that single inject ions of beta A4 impair memory consolidation, but repeated injections o f beta A4 over an extended period do not affect well-learned behavior. (C) 1994 Academic Press, Inc.