ArticleGenes, brain, and behavior2012
A new model of Pde4d deficiency: genetic knock-down of PDE4D enzyme in rats produces an antidepressant phenotype without spatial cognitive effects.
Article in Genes, brain, and behavior, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Ginkgo Biloba as a niche theme cognitive enhancer agent, 1420 dokumen of Scopus database. A bibliometric study from 1988 to 2024.F1000Research · 2025Article
- Tests for learning and memory in rodent regulatory studies.Current research in toxicology · 2024Article
- Phosphodiesterase inhibitors in psychiatric disorders.Psychopharmacology · 2023Review
- PAN-selective inhibition of cAMP-phosphodiesterase 4 (PDE4) induces gastroparesis in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Dominant-Negative Attenuation of cAMP-Selective Phosphodiesterase PDE4D Action Affects Learning and Behavior.International journal of molecular sciences · 2020Article
- Fear renewal activates cyclic adenosine monophosphate signaling in the dentate gyrus.Brain and behavior · 2019Article
- A negative allosteric modulator of PDE4D enhances learning after traumatic brain injury.Neurobiology of learning and memory · 2018Article
- Altered phosphorylation, electrophysiology, and behavior on attenuation of PDE4B action in hippocampus.BMC neuroscience · 2017Article
- Phosphodiesterase-1b deletion confers depression-like behavioral resistance separate from stress-related effects in mice.Genes, brain, and behavior · 2017Article
- Phosphodiesterase-1b (Pde1b) knockout mice are resistant to forced swim and tail suspension induced immobility and show upregulation of Pde10a.Psychopharmacology · 2017Article
- Chronic Cognitive Dysfunction after Traumatic Brain Injury Is Improved with a Phosphodiesterase 4B Inhibitor.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Intranasal midazolam administration enhances amnesic effect in rats.Journal of anesthesia · 2016Article
- Phosphodiesterase-4D Knock-down in the Prefrontal Cortex Alleviates Chronic Unpredictable Stress-Induced Depressive-Like Behaviors and Memory Deficits in Mice.Scientific reports · 2015Article
- Proof-of-Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin) Targeting Phosphodiesterase-4 in Cognitively Healthy Subjects: Implications for Alzheimer's Dementia.Evidence-based complementary and alternative medicine : eCAM · 2014Article
- PDE4 as a target for cognition enhancement.Expert opinion on therapeutic targets · 2013Review
- DISC1-ATF4 transcriptional repression complex: dual regulation of the cAMP-PDE4 cascade by DISC1.Molecular psychiatry · 2013Article
- Cincinnati water maze: A review of the development, methods, and evidence as a test of egocentric learning and memory.Neurotoxicology and teratologyReview
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Phosphodiesterases (PDEs) are a superfamily of intracellular second messenger cyclic nucleotide hydrolyzing enzymes composed of 12 families. The Pde4 family has been implicated in depression and cognition, and PDE4 inhibitors have been evaluated as antidepressants and possible cognitive enhancers. Pde4d(-/-) mice show an antidepressant phenotype and learning enhancement on some tests, but not others as do mice treated with PDE4 inhibitors. Here, we report for the first time the behavioral phenotype of a new Pde4d knock-down (KD) rat model of PDE4D deficiency. Consistent with other data on PDE4D deficiency, Pde4d KD rats showed depression resistance in the Porsolt forced swim test and hyperreactivity of the acoustic startle response with no differential response on prepulse inhibition, suggesting no sensorimotor gating defect. Pde4d KD rats also exhibited a small exploratory activity reduction but no difference following habituation, and no enhanced spatial learning or reference memory in the Morris water maze. A selective improvement in route-based learning in the Cincinnati water maze was seen as well as enhanced contextual and cued fear conditioning and a more rapid rate of cued extinction from their higher freezing level that declined to wild-type (WT) levels only after ∼20 extinction trials. The rat model confirms Pde4d's role in depression but not in spatial learning or memory enhancement and shows for the first time higher fear conditioning and altered extinction compared with controls. The new model provides a tool by which to better understand the role of PDE4D in neuropsychiatric disorders and for the development of alternate treatment approaches.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.