ArticleThe Journal of pharmacology and experimental therapeutics2008
Reversal of oxidative stress-induced anxiety by inhibition of phosphodiesterase-2 in mice.
Article in The Journal of pharmacology and experimental therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 220 citations in OpenAlex.
- Activation of TLR4 promotes oxidative inflammation via NADPH oxidase signaling in platelets of subjects with autism spectrum disorder.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Article
- Modulating the Bioavailability and Bioaccessibility of Polyphenolic Compounds and Enhancing Health-Promoting Properties Through the Addition of Herbal Extracts to a Functional Beverage.Molecules (Basel, Switzerland) · 2025Article
- Ambroxol's Role in PTZ-Induced Anxiety-Like Conditions in Mice: Targeting Neuroinflammation and Oxidative Stress via In Vivo and In Silico Approaches.Molecular neurobiology · 2025Article
- IRF8 deficiency causes anxiety-like behavior in a sex-dependent manner.bioRxiv : the preprint server for biology · 2025Article
- Longevity, enhanced memory, and altered density of dendritic spines in hippocampal CA3 and dentate gyrus after hemizygous deletion of Pde2a in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Apocynin Prevents Cigarette Smoke-Induced Anxiety-Like Behavior and Preserves Microglial Profiles in Male Mice.Antioxidants (Basel, Switzerland) · 2024Article
- Brain oxidative stress mediates anxiety-like behavior induced by indomethacin in zebrafish: protective effect of alpha-tocopherol.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Menopause-Associated Depression: Impact of Oxidative Stress and Neuroinflammation on the Central Nervous System-A Review.Biomedicines · 2024Review
- Oxidative Stress is a New Avenue for Treatment of Neuropsychiatric Disorders: Hype of Hope?Current molecular medicine · 2024Review
- Recent Advances in the Synthesis of Antioxidant Derivatives: Pharmacological Insights for Neurological Disorders.Current topics in medicinal chemistry · 2024Review
- Therapeutic potential of NOX inhibitors in neuropsychiatric disorders.Psychopharmacology · 2023Review
- Characterization of 2 Novel Phosphodiesterase 2 Inhibitors Hcyb1 and PF-05180999 on Depression- and Anxiety-Like Behavior.The international journal of neuropsychopharmacology · 2023Article
- Phosphodiesterase inhibitors in psychiatric disorders.Psychopharmacology · 2023Review
- Understanding the Role of Oxidative Stress, Neuroinflammation and Abnormal Myelination in Excessive Aggression Associated with Depression: Recent Input from Mechanistic Studies.International journal of molecular sciences · 2023Review
- Melatonin as a Potential Approach to Anxiety Treatment.International journal of molecular sciences · 2022Review
- Alcohol Withdrawal and the Associated Mood Disorders-A Review.International journal of molecular sciences · 2022Review
- "K-Powder" Exposure during Adolescence Elicits Psychiatric Disturbances Associated with Oxidative Stress in Female Rats.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Broccoli Sprouts Promote Sex-Dependent Cardiometabolic Health and Longevity in Long-Evans Rats.International journal of environmental research and public health · 2022Article
- Behavioral and Cognitive Consequences of Obesity in Parents and Offspring in Female and Male Rats: Implications of Neuroinflammation and Neuromodulation.Molecular neurobiology · 2022Article
- Circulating Human Serum Metabolites Derived from the Intake of a Saffron Extract (Safr'InsideNutrients · 2022Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The pathogenesis of several neuropsychiatric disorders, including anxiety and depression, has been linked to oxidative stress, in part via alterations in cyclic nucleotide signaling. Phosphodiesterase-2 (PDE2), which regulates cGMP and cAMP signaling, may affect anxiety-related behavior through reduction of oxidative stress. The present study evaluated the effects of oxidative stress on behavior and assessed the anxiolytic effects of the PDE2 inhibitor Bay 60-7550 [(2-(3,4-dimethoxybenzyl)-7-{(1R)-1-[(1R)-1-hydroxyethyl]-4-phenylbutyl}-5-methyl imidazo-[5,1-f][1,2,4]triazin-4(3H)-one)]. Treatment of mice with L-buthionine-(S,R)-sulfoximine (300 mg/kg), an inducer of oxidative stress, caused anxiety-like behavioral effects in elevated plusmaze, open-field, and hole-board tests through the NADPH oxidase pathway; these effects were antagonized by Bay 60-7550 (3 mg/kg) and apocynin (3 mg/kg), an inhibitor of NADPH oxidase. The Bay 60-7550-mediated decrease in oxidative stress (i.e., superoxide anion and reactive oxygen species generation in cultured neurons and total antioxidant capacity and lipid peroxides in amygdala and hypothalamus) and expression of NADPH oxidase subunits (i.e., p47 phox and gp91 phox expression in amygdala, hypothalamus, and cultured neurons) was associated with increased cGMP and phosphorylation of vasodilator-stimulated phosphoprotein at Ser239, suggesting an important role of cGMP-protein kinase G signaling in reduction of anxiety. Overall, the present results indicate that oxidative stress induces anxiety-like behavior in mice and that PDE2 inhibition reverses it through an increase in cGMP signaling. Thus, PDE2 may be a novel pharmacological target for treatment of anxiety in neuropsychiatric and neurodegenerative disorders that involve oxidative stress.
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