ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2008
Anxiogenic-like behavioral phenotype of mice deficient in phosphodiesterase 4B (PDE4B).
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 174 citations in OpenAlex.
- Variations in alcohol craving and negative mood during a clinical trial of ibudilast for alcohol use disorder.Alcohol, clinical & experimental research · 2025Trial
- Pde4 mediates MHCII expression in oligodendroglia.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Subanesthetic doses of ketamine to rats and monkeys rapidly increases radioligand binding in brain to phosphodiesterase-4, an indirect marker of cAMP.Translational psychiatry · 2026Article
- The Emerging Role of Phosphodiesterase Inhibitors in Fragile X Syndrome and Autism Spectrum Disorder.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Differential effects of Phosphodiesterase 4A5 on cAMP-dependent forms of long-term potentiation.The Journal of physiology · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Engineered Extracellular Vesicles Modified by Angiopep-2 Peptide Promote Targeted Repair of Spinal Cord Injury and Brain Inflammation.ACS nano · 2025Article
- Phosphodiesterase 4 Inhibition in Neuropsychiatric Disorders Associated with Alzheimer's Disease.Cells · 2025Review
- Potential of phosphodiesterase 4B inhibitors in the treatment of interstitial lung disease associated with autoimmune diseases.Clinical and experimental rheumatology · 2025Review
- Real-world safety profile of roflumilast: a pharmacovigilance analysis using FDA adverse event reporting system and Canada vigilance database.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2025Article
- Selective PDE4B and PDE4D inhibitors produce distinct behavioral responses to ethanol and GABAergic drugs in mice.Neuropharmacology · 2023Article
- Phosphodiesterase 4B inhibition: a potential novel strategy for treating pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2023Review
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- Apremilast-induced increases in acute ethanol intoxication and decreases in ethanol drinking in mice involve PKA phosphorylation of GABANeuropharmacology · 2022Article
- Selective Inhibition of PDE4B Reduces Methamphetamine Reinforcement in Two C57BL/6 Substrains.International journal of molecular sciences · 2022Article
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- Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders.Molecular psychiatry · 2021Review
- Recent developments and potential of robotics in plant eco-phenotyping.Emerging topics in life sciences · 2021Article
- Selective Inhibition of PDE4B Reduces Binge Drinking in Two C57BL/6 Substrains.International journal of molecular sciences · 2021Article
38 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Phosphodiesterase-4 (PDE4), an enzyme that catalyzes the hydrolysis of cyclic AMP and plays a critical role in controlling its intracellular concentration, has been implicated in depression- and anxiety-like behaviors. However, the functions of the four PDE4 subfamilies (PDE4A, PDE4B, PDE4C, and PDE4D) remain largely unknown. In animal tests sensitive to anxiolytics, antidepressants, memory enhancers, or analgesics, we examined the behavioral phenotype of mice deficient in PDE4B (PDE4B-/-). Immunoblot analysis revealed loss of PDE4B expression in the cerebral cortex and amygdala of PDE4B-/- mice. The reduction of PDE4B expression was accompanied by decreases in PDE4 activity in the brain regions of PDE4B-/- mice. Compared to PDE4B+/+ littermates, PDE4B-/- mice displayed anxiogenic-like behavior, as evidenced by decreased head-dips and time spent in head-dipping in the holeboard test, reduced transitions and time on the light side in the light-dark transition test, and decreased initial exploration and rears in the open-field test. Consistent with anxiogenic-like behavior, PDE4B-/- mice displayed increased levels of plasma corticosterone. In addition, these mice also showed a modest increase in the proliferation of neuronal cells in the hippocampal dentate gyrus. In the forced-swim test, PDE4B-/- mice exhibited decreased immobility; however, this was not supported by the results from the tail-suspension test. PDE4B-/- mice did not display changes in memory, locomotor activity, or nociceptive responses. Taken together, these results suggest that the PDE4B subfamily is involved in signaling pathways that contribute to anxiogenic-like effects on behavior.
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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.