Post-training intrahippocampal infusion of protein kinase C inhibitors causes amnesia in rats

Abstract

This experiment investigated the effect on memory, in rats, of the bilateral intrahippocampal post-training infusion of two different inhibitors of protein kinase C activity, staurosporin and CGP41231. Male Wistar rats were implanted bilaterally with cannulae aimed at the CA1 region of the dorsal hippocampus. After recovery from surgery, they were trained in step-down inhibitory avoidance using a 0.5-mA footshock and tested for retention 24 h later. Immediately or 30, 120, or 180 min after training they received, through the cannulae, infusions of vehicle, staurosporin (1.0 μg), or CGP41231 (2.5 μg). The two drugs caused full retrograde amnesia when given immediately or 30 min post-training, partial amnesia when given 120 min after training, and had no effect when given 180 min after training. The results support the suggestion that memory involves long-term potentiation initiated at the time of training in the hippocampus. Inhibitors of protein kinase C block the development of long-term potentiation when administered in the first 2 h after induction.