Reversal of beta-amyloid-induced retention deficit after exposure to training and state cues

We explored amnesia induced by posttraining injection of beta-amyloid protein (beta A4) in four experiments. Previous reports showed that beta A4 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 beta A4 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 beta A4(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 beta A4(40-1) group was unimpaired. Experiments 2 and 3 attempted to reverse the amnestic effects of beta A4 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 beta A4-induced amnesia. In Experiment 4, beta A4-induced impairments were reversed by reinjecting beta A4 immediately before retention testing. Results indicate that beta A4 injected after partial training does not interfere with a consolidation process. (C) 1996 Acdaemic Press, Inc.