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 re cently proposed to participate in both the late phase of long term pot entiation in the hippocampus and in the late, protein synthesis-depend ent phase of memory formation, Here we report that a late memory conso lidation 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 hip pocampus, 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 c ontrast, full retrograde amnesia was obtained when SCH 23390 (0.5 mu g /side), a D-1/D-5 receptor antagonist, was infused into the hippocampu s 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 cy clase, enhanced memory when given 3 or 6 h after training, KT5720 (0.5 mu g/side), a specific inhibitor of PKA, hindered memory consolidatio n when given immediately or 3 or 6 h posttraining, Rats submitted to t he avoidance task showed learning-specific increases in hippocampal H- 3-SCH 23390 binding and in the endogenous levels of cAMP 3 and 6 h aft er training, In addition, PKA activity and P-CREB (phosphorylated form of cAMP responsive element binding protein) immunoreactivity increase d in the hippocampus immediately and 3 and 6 h after training. Togethe r, these findings suggest that the late phase of memory consolidation of an inhibitory avoidance is modulated cAMP/PKA signaling pathways in the hippocampus.