title: A phosphodiesterase 4-controlled switch between memory extinction and strengthening in the hippocampus.
abstract: Established fear-related memories can undergo phenomena such as extinction or reconsolidation when recalled. Extinction probably involves the creation of a new, competing memory trace that decreases fear expression, whereas reconsolidation can mediate memory maintenance, updating, or strengthening. The factors determining whether retrieval will initiate extinction, reconsolidation, or neither of these two processes include training intensity, duration of the retrieval session, and age of the memory. However, previous studies have not shown that the same behavioral protocol can be used to induce either extinction or reconsolidation and strengthening, depending on the pharmacological intervention used. Here we show that, within an experiment that leads to extinction in control rats, memory can be strengthened if rolipram, a selective inhibitor of phosphodiesterase type 4 (PDE4), is administered into the dorsal hippocampus immediately after retrieval. The memory-enhancing effect of rolipram lasted for at least 1 week, was blocked by the protein synthesis inhibitor anisomycin, and did not occur when drug administration was not paired with retrieval. These findings indicate that the behavioral outcome of memory retrieval can be pharmacologically switched from extinction to strengthening. The cAMP/protein kinase A (PKA) signaling pathway might be a crucial mechanism determining the fate of memories after recall.
authors.affiliation: Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul Porto Alegre, Brazil ; Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul Porto Alegre, Brazil ; National Institute for Translational Medicine (INCT-TM) Porto Alegre, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Roesler
authors.affiliation: Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul Porto Alegre, Brazil ; Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul Porto Alegre, Brazil ; National Institute for Translational Medicine (INCT-TM) Porto Alegre, Brazil.
authors.forename: Gustavo K
authors.initials: GK
authors.lastname: Reolon
authors.affiliation: Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul Porto Alegre, Brazil ; Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul Porto Alegre, Brazil ; National Institute for Translational Medicine (INCT-TM) Porto Alegre, Brazil.
authors.forename: Natasha
authors.initials: N
authors.lastname: Maurmann
authors.affiliation: Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul Porto Alegre, Brazil ; National Institute for Translational Medicine (INCT-TM) Porto Alegre, Brazil ; Department of Internal Medicine, School of Medicine, Federal University of Rio Grande do Sul Porto Alegre, Brazil.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Schwartsmann
authors.affiliation: National Institute for Translational Medicine (INCT-TM) Porto Alegre, Brazil ; Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University Porto Alegre, Brazil.
authors.forename: Nadja
authors.initials: N
authors.lastname: Schröder
authors.affiliation: Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro Rio de Janeiro, Brazil.
authors.forename: Olavo B
authors.initials: OB
authors.lastname: Amaral
authors.affiliation: National Institute for Translational Medicine (INCT-TM) Porto Alegre, Brazil ; Laboratory of Neurosciences, Graduate Program in Health Sciences, Academic Unit of Health Sciences, University of Southern Santa Catarina (UNESC) Criciúma, Brazil.
authors.forename: Samira
authors.initials: S
authors.lastname: Valvassori
authors.affiliation: National Institute for Translational Medicine (INCT-TM) Porto Alegre, Brazil ; Laboratory of Neurosciences, Graduate Program in Health Sciences, Academic Unit of Health Sciences, University of Southern Santa Catarina (UNESC) Criciúma, Brazil ; Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston Houston, TX, USA.
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
keywords: extinction; fear memory; hippocampus; inhibitory avoidance; phosphodiesterase 4; reconsolidation; rolipram