Intrahippocampal or intraamygdala infusion of KN62, a specific inhibitor of calcium/calmodulin-dependent protein kinase II, causes retrograde amnesia in the rat.

We investigated the effect of a bilateral post-training intracerebral infusion of KN62, a specific inhibitor of calcium/calmodulin-dependent protein kinase II (CaM-II), on memory. This enzyme plays a crucial role in the early phases of long-term potentiation. Male Wistar rats were implanted bilaterally with cannulae aimed at the CA1 region of the dorsal hippocampus or at the junction between the central and the basolateral nuclei of the amygdala. After recovery, rats were trained in step-down inhibitory avoidance using a 0.5-mA footshock and tested for retention 24 h later. At various times after training (0, 30, 120, or 240 min for the animals implanted into the hippocampus; 0 or 240 min for the animals implanted in the amygdala) they received, through the cannulae, an infusion of vehicle (0.1% dimethylsulfoxide in water) or KN62 (100 mumol/side). KN62 caused full retrograde amnesia when given 0 min after training into either the amygdala or the hippocampus. When given into the hippocampus 30 min post-training it had a partial amnestic effect. When given 120 min after training into the hippocampus, or 240 min after training into either structure, KN62 had no effect. The data suggest that the early phase of memory requires intact CaM-II activity in the amygdala and hippocampus and support the hypothesis that memory involves long-term potentiation initiated at the time of training in both structures.