Stimulators of the cAMP cascade reverse amnesia induced by intra-amygdala but not intrahippocampal KN-62 administration

Infusion of the calcium-calmodulin-dependent protein kinase II (CaMKII) inh ibitor KN-62 (3.5 ng/side) 0 h after training into rat hippocampus CA1 or a mygdala has been known for years to cause retrograde amnesia for step-down inhibitory avoidance. On the other hand, drugs that indirectly stimulate pr otein kinase A (PKA) (8-Br-cAMP, 1.25 mu g/side; norepinephrine, 0.3 mu g/s ide; the dopamine D1 receptor agonist, SKF38393, 7.5 mu g/side) infused 3 h posttraining into CAI but not amygdala markedly facilitate retention of th is task. Here we find that 8-Br-cAMP, norepinephrine, or SKF38393 given 3 h posttraining into rat CA1 reverses the amnestic effect of KN-62 given into the amygdala 0 h after training, but not that of KN-62 given into CA1 0 h posttraining. The findings bear on the participation of CaMKII and of the c AMP/PKA cascade in memory processes in the hippocampus and the amygdala. Bo th cascades have been proposed to play a role in memory: CaMKII in the earl y phase and PKA in the transition between the early phase and long-term mem ory. Clearly, in CA1, both cascades are involved and are crucial, and the C aMKII cascade must precede the PKA cascade. In contrast, in the amygdala, o nly the CaMKII. cascade is active, and it does not play a central role in m emory, inasmuch as its deleterious effect may be fully recovered by stimula tion of the PKA cascade in the hippocampus. This further supports the conte ntion that the hippocampus is essential for memory formation of this task, as it is for many others, whereas the amygdala appears to play instead an e arly modulatory role. (C) 1999 Academic Press.