ArticleBrain and behavior2019
Fear renewal activates cyclic adenosine monophosphate signaling in the dentate gyrus.
Article in Brain and behavior, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 8 citations in OpenAlex.
- Parietal-Frontal Pathway Controls Relapse of Fear Memory in a Novel Context.Biological psychiatry global open science · 2024Article
- Cilostazol pretreatment prevents PTSD-related anxiety behavior through reduction of hippocampal neuroinflammation.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Phosphodiesterase 4 inhibition after retrieval switches the memory fate favoring extinction instead of reconsolidation.Scientific reports · 2023Article
- Phosphodiesterase inhibitors in psychiatric disorders.Psychopharmacology · 2023Review
- Behavioral pattern separation is associated with neural and electrodermal correlates of context-dependent fear conditioning.Scientific reports · 2023Article
- Inhibition of Phosphodiesterase 2 Ameliorates Post-Traumatic Stress-Induced Alcohol Intake Disorder by Regulating cAMP/cGMP Signaling.The international journal of neuropsychopharmacology · 2022Article
- Fear renewal activates cyclic adenosine monophosphate signaling in the dentate gyrus.Brain and behavior · 2019Article
- Individual contribution of PDE4B and PDE4D subfamilies to the prevention of object location memory impairments induced by sleep deprivation.Learning & memory (Cold Spring Harbor, N.Y.)Article
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5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundFear renewal, the context-specific relapse of a conditioned fear after extinction, is a widely pursued model of post-traumatic stress disorder and phobias. However, its cellular and molecular mechanisms remain poorly understood. The dentate gyrus (DG) has emerged as a critical locus of plasticity with relevance to memory, anxiety disorders, and depression, and it contributes to fear memory retrieval. Here, we have identified the role of the DG in fear renewal and its molecular mechanism. MATERIALS AND
methodsMuscimol (MUS), activator of cyclic adenosine monophosphate (cAMP) forskolin (FSK), inhibitor of protein kinase A (PKA), Rip-cAMP, and a phosphodiesterase inhibitor rolipram were infused into DG of standard deviation rats before renewal testing. cAMP levels after fear renewal was measured by enzyme-linked immunosorbent assay. The protein levels of phosphodiesterase 4 (PDE4) isoforms were tested by western blot. At last, the roles of cAMP signaling were also tested in the acquisition of fear conditioning, fear retrieval, and extinction.
resultsIntra-DG treatment of MUS and Rp-cAMP impaired fear renewal. FSK and rolipram exhibited the opposite effect, which also occurred in the retrieval of original fear memory. This change in fear renewal was regulated by PDE4 isoforms PDE4A, PDE4A5, and PDE4D. In addition, FSK and rolipram facilitated the acquisition of fear conditioning in long-term memory, but not short-term memory, while Rp-cAMP impaired long-term memory. For extinction, FSK and rolipram inhibited extinction process, while Rp-cAMP facilitated fear extinction.
conclusionThese findings demonstrated that fear renewal activated cAMP signaling in the DG through decreased PDE4 activity. Because of the role of cAMP signaling in the acquisition or retrieval of fear conditioning and encoding of extinction, it is speculated that initial learning and extinction may have similarities in molecular mechanism, especially fear retrieval and fear renewal may share cAMP signaling pathway in the DG.
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