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

BERNABEU, R., BEVILAQUA, L., ARDENGHI, P., BROMBERG, E., SCHMITZ, P., BIANCHIN, M., IZQUIERDO, I. & MEDINA, J.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Año: 1997 vol. 94 p. 7041 - 7046

0027-8424

ABSTRACT cAMPycAMP-dependent protein kinase(PKA) signaling pathway has been recently proposed toparticipate in both the late phase of long term potentiation inthe hippocampus and in the late, protein synthesis-dependentphase of memory formation. Here we report that a latememory consolidation phase of an inhibitory avoidance learningis regulated by an hippocampal cAMP signaling pathwaythat is activated, at least in part, by D1yD5 receptors. Bilateralinfusion of SKF 38393 (7.5 mgyside), a D1yD5 receptor agonist,into the CA1 region of the dorsal hippocampus, enhancedretention of a step-down inhibitory avoidance when given 3 or6 h, but not immediately (0 h) or 9 h, after training. Incontrast, full retrograde amnesia was obtained when SCH23390 (0.5 mgyside), a D1yD5 receptor antagonist, was infusedinto the hippocampus 3 or 6 h after training. Intrahippocampalinfusion of 8Br-cAMP (1.25 mgyside), or forskolin (0.5mgyside), an activator of adenylyl cyclase, enhanced memorywhen given 3 or 6 h after training. KT5720 (0.5 mgyside), aspecific inhibitor of PKA, hindered memory consolidationwhen given immediately or 3 or 6 h posttraining. Ratssubmitted to the avoidance task showed learning-specificincreases in hippocampal 3H-SCH 23390 binding and in theendogenous levels of cAMP 3 and 6 h after training. Inaddition, PKA activity and P-CREB (phosphorylated form ofcAMP responsive element binding protein) immunoreactivityincreased in the hippocampus immediately and 3 and 6 h aftertraining. Together, these findings suggest that the late phaseof memory consolidation of an inhibitory avoidance is modulatedcAMPyPKA signaling pathways in the hippocampus.