Possible Underlying Influence of p38MAPK and NF-κB in the Diminished Anti-anxiety Effect of Diazepam in Stressed Mice
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The present study was designed to explore the possible nitriergic influence and role of p38MAPK and NF-κB in the diminished anti-anxiety effect of diazepam in stressed mice, using the elevated plus maze and light/dark box to assess anxiety. Immobilization stress for 6 h enhanced an anxiety-like behavior and increased plasma nitrite levels in mice. Diazepam (2 mg/kg, i.p.) produced an anti-anxiety effect in unstressed mice, but could not produce any change in anxiety levels of stressed mice. SB-203580 (2 mg/kg, i.p.), a specific inhibitor of p38MAPK, per se produced a significant antianxiety-like activity in stressed mice. Administration of a combination of SB-203580 (2 mg/kg, i.p.) and diazepam (2 mg/kg) in stressed mice produced a significantly higher antianxiety-like activity than that produced by SB-203580 alone. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of the activation of NF-κB, per se produced a significant antianxiety-like activity in stressed mice. Combination of PDTC and diazepam also served to produce a higher significant antianxiety-like activity in stressed mice than that produced by PDTC alone. Diazepam could not produce any change in plasma nitrite levels in both unstressed and stressed mice. Both SB-203580 (2 mg/kg, i.p.) and PDTC (100 mg/kg, i.p.) significantly decreased plasma nitrite levels in stressed mice. The observations indicate that the diminished anti-anxiety effect of diazepam in stressed mice may involve strong nitriergic influence and may further be p38MAPK- and NF-κB-dependent.
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The senescence stress response allows damaged cells to survive by upregulating senescent cell anti-apoptotic pathways and causes inflammation through the senescence-associated secretory phenotype.
“The senescence stress response allows damaged cells to survive by upregulating senescent cell anti-apoptotic pathways (SCAPs)10 and causes inflammation through their senescence-associated secretory phenotype (SASP)11,12.”
From Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial (2023) · cites this paper as [12]
The Introduction and Discussion address immobilization stress, anxiety, p38MAPK, NF-κB, and nitric oxide signaling in mice, not cellular senescence. Searches for senescent-cell anti-apoptotic pathways and the senescence-associated secretory phenotype found no passage supporting either mechanism; the citation placed after SCAPs is therefore not substantiated by our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredThe senescence-associated secretory phenotype is dependent on p38MAPK, NF-κB, cGAS/STING, NOTCH and mTOR signalling.
“Another key feature of cellular senescence is the senescence-associated secretory phenotype (SASP), which is dependent on p38MAPK (p38 mitogen-activated protein kinases), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), cGAS(cyclic GMP-AMP synthase)/STING(stimulator of IFN genes), NOTCH and mTORmammalian target of rapamycin) signalling [38,39,40,41,42].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [41]
Senescent cells can develop a senescence-associated secretory phenotype through dysregulation of p38MAPK, NF-κB, NOTCH, and mTOR signaling.
“Through dysregulation of p38 mitogen-activated protein kinases (p38MAPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), NOTCH, and mammalian target of rapamycin (mTOR) signaling, senescent cells can develop a senescence-associated secretory phenotype (SASP) (22, 23).”
From Senolytic Therapy to Modulate the Progression of Alzheimer's Disease (SToMP-AD): A Pilot Clinical Trial (2022) · cites this paper as [23]
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References 51 · Cited by 31
Research works printed but not linked: 2
- Zie QW, Kashiwabara Y, Nathan C. Role of NFkB/Rel in induc- tion of nitric oxide synthase. J Biol Chem. 1994;269:4705- 4708.
- Serre M, Concas A, Astogglu T, Biggio G. Stress-like bicuculine and DMCM reduces the basal 36 Cl -uptake in the rat cortical membrane vesicles: an effect reversed by GABA. Neurosci Res Commun. 1989;4:41-50.
- Authors
- Sharma, V., Gilhotra, R., Dhingra, D., & Gilhotra, N.
- Affiliations
- Gyan Vihar University (IN)
- Guru Jambheshwar University of Science and Technology (IN)
- Maharshi Dayanand University (IN)
- Venue
- Journal of Pharmacological Sciences
- Publisher
- Japanese Pharmacological Society
- Published
- 2011
- Volume
- 116
- Issue
- 3
- Pages
- 257-263
- ISSN
- 1347-8613 (ISSN-L)
- 1347-8648
- OpenAlex
- W2081286059
- Cited by
- 31
- References
- 51
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2021: 4 · 2020: 3 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 2
- FWCI
- 0.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Pharmacological Sciences (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- diazepam, anxiety, restraint stress, p38 MAPK, NF-κB, nitric oxide, nitric oxide synthase, SB203580, pyrrolidine dithiocarbamate, anxiolytic effects, plasma nitrite, stress-induced anxiety
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Diazepam, Drug Resistance, Drug Synergism, Exploratory Behavior, Imidazoles, Male, Nitrites, Pyridines, Pyrrolidines, Restraint, Physical, Stress, Physiological, Stress, Psychological, Thiocarbamates, Anti-Anxiety Agents, NF-kappa B, GABA Agonists, Protein Kinase Inhibitors, p38 Mitogen-Activated Protein Kinases, Mice
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