We explored amnesia induced by posttraining injection of β-amyloid protein (βA4) in four experiments. Previous reports showed that βA4 impaired retention of learning maintained either by food reward or by shock relief. The experiments in this paper attempted to determine (1) if the amnesia is specific to the 1-40 βA4 amino-acid sequence; and (2) if the amnesia can be attributed to a consolidation process. Subjects were 190 male Sprague-Dawley rats, 3 to 6 months old. Subjects were given five training trials on a left-right discrimination in a Y-maze with a food reward and injected immediately afterward with βA4(1-40) or vehicle. One week later they were trained to criterion. Experiment 1 used a control group that was injected with the reverse-sequence peptide (40-1). The performance of the βA4(40-1) group was unimpaired. Experiments 2 and 3 attempted to reverse the amnestic effects of βA4 using noncontingent presentation of aspects of the training context during the retention interval. Experimental subjects in Experiment 2 were exposed to the Y-maze in the absence of reinforcers, 24, 22, and 2 h before retention testing. In Experiment 3, subjects were given a 1-min exposure to the reinforcers, outside the Y-maze, 24 h before retention testing. Both manipulations reversed βA4-induced amnesia. In Experiment 4, βA4-induced impairments were reversed by reinjecting βA4 immediately before retention testing. Results indicate that βA4 injected after partial training does not interfere with a consolidation process.
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1 This work was supported by a Department of Veterans Affairs Merit Review grant awarded to J.C. and an American Psychological Association Doctoral Dissertation Fellowship Award to M.M. M.M. was supported under NICHD Training Grant T32 HD07279 and completed this research in partial ful®llment of the degree of Doctor of Philosophy at the University of Minnesota. 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 correspondence and reprint requests to Mike McDonald, Ph.D., National Institute