title: Possible underlying influence of p38MAPK and NF-κB in the diminished anti-anxiety effect of diazepam in stressed mice.
abstract: 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.
authors: School of Pharmacy, Gyan Vihar University, Jaipur, Rajasthan, India.
authors: Vipin
authors: V
authors: Sharma
authors: Ritu
authors: R
authors: Gilhotra
authors: Dinesh
authors: D
authors: Dhingra
authors: Neeraj
authors: N
authors: Gilhotra
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D001522:Behavior, Animal / Q000187:drug effects; D003975:Diazepam / Q000627:therapeutic use*; D004351:Drug Resistance; D004357:Drug Synergism; D005106:Exploratory Behavior / Q000187:drug effects; D018755:GABA Agonists / Q000627:therapeutic use*; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011759:Pyrrolidines / Q000627:therapeutic use; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000187:drug effects; D013315:Stress, Psychological / Q000503:physiopathology; D013859:Thiocarbamates / Q000627:therapeutic use; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; D018755:GABA Agonists; D007093:Imidazoles; D016328:NF-kappa B; D009573:Nitrites; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D003975:Diazepam