Possible underlying influence of p38MAPK and NF-κB in the diminished anti-anxiety effect of diazepam in stressed mice

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 antianxietylike 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. © the japanese pharmacological society.