title: A cAMP analog reverses contextual and tone memory deficits induced by a PKA inhibitor in Pavlovian fear conditioning.
abstract: 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 24h and 48h after training respectively. Bilateral infusion of 100 and 300μM/side of bucladesine immediately after training increased freezing percentage in rats, which indicated an improvement in memory consolidation. Administration of 10μM/side (but not 5μM/side) of H-89 impaired contextual and cued fear conditioning significantly compared to the control animals. Moreover, administration of bucladesine (100 and 300μM/side), 5min after H-89 infusion (10μM/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.
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Nassireslami
authors.forename: Parmida
authors.initials: P
authors.lastname: Nikbin
authors.forename: Borna
authors.initials: B
authors.lastname: Payandemehr
authors.forename: Elham
authors.initials: E
authors.lastname: Amini
authors.forename: Mojdeh
authors.initials: M
authors.lastname: Mohammadi
authors.forename: Glareh
authors.initials: G
authors.lastname: Vakilzadeh
authors.forename: Tahereh
authors.initials: T
authors.lastname: Ghadiri
authors.forename: Farshid
authors.initials: F
authors.lastname: Noorbakhsh
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sharifzadeh
mesh_terms: D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003214:Conditioning, Classical; D000242:Cyclic AMP / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D005239:Fear; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D007546:Isoquinolines; D013449:Sulfonamides; D003994:Bucladesine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide