A cAMP analog reverses contextual and tone memory deficits induced by a PKA inhibitor in Pavlovian fear conditioning

Despite extensive investigations, molecular mechanisms underlying the formation of fear memory are not completely understood. We have previously investigated the role of protein kinase AII (PKAII) in spatial acquisition and memory retention using Morris water maze. In the current study, we have further analyzed the role of PKA in memory consolidation using a fear conditioning response model. Experiments were performed using intrahippocampal infusions of dibutyryl cyclic AMP (bucladesine), a cell permeable analog of cAMP and H89, as a selective PKAII inhibitor, in male rats. The animals were trained for one session which included 4 consecutive trials of tone-shock pairing on the training day.Fear to the context and tone was evaluated by measuring freezing behavior 24 h and 48 h after training respectively. Bilateral infusion of 100 and 300 μM/side of bucladesine immediately after training increased freezing percentage in rats, which indicated an improvement in memory consolidation. Administration of 10 μM/side (but not 5 μM/side) of H-89 impaired contextual and cued fear conditioning significantly compared to the control animals. Moreover, administration of bucladesine (100 and 300 μM/side), 5 min after H-89 infusion (10 μM/side) reversed the impairment of contextual and auditory-cued fear conditioning in rats and freezing percentage increased to those of control animals.Altogether, these results indicate that PKA inhibitor-induced memory deficit was attenuated by a cAMP analog and that the cAMP/PKA signaling pathway has an important role for memory consolidation in fear conditioning response model.