Involvement of hippocampal cAMP/cAMP-dependent protein kinase signaling pathways in a late memory consolidation phase of aversively motivated learning in rats

cAMP/cAMP-dependent protein kinase (PKA) signaling pathway has been recently proposed to participate in both the late phase of long term potentiation in the hippocampus and in the late, protein synthesis-dependent phase of memory formation, Here we report that a late memory consolidation phase of an inhibitory avoidance learning is regulated by an hippocampal cAMP signaling pathway that is activated, at least in part, by D-1/D-5 receptors, Bilateral infusion of SKF 38393 (7.5 mu g/side), a D-1/D-5 receptor agonist, into the CA(1) region of the dorsal hippocampus, enhanced retention of a step-down inhibitory avoidance when given 3 or 6 h, but not immediately (0 h) or 9 h, after training, In contrast, full retrograde amnesia was obtained when SCH 23390 (0.5 mu g/side), a D-1/D-5 receptor antagonist, was infused into the hippocampus 3 or 6 h after training, Intrahippocampal infusion of 8Br-cAMP (1.25 mu g/side), or forskolin (0.5 mu g/side), an activator of adenylyl cyclase, enhanced memory when given 3 or 6 h after training, KT5720 (0.5 mu g/side), a specific inhibitor of PKA, hindered memory consolidation when given immediately or 3 or 6 h posttraining, Rats submitted to the avoidance task showed learning-specific increases in hippocampal H-3-SCH 23390 binding and in the endogenous levels of cAMP 3 and 6 h after training, In addition, PKA activity and P-CREB (phosphorylated form of cAMP responsive element binding protein) immunoreactivity increased in the hippocampus immediately and 3 and 6 h after training. Together, these findings suggest that the late phase of memory consolidation of an inhibitory avoidance is modulated cAMP/PKA signaling pathways in the hippocampus.