GABAergic and nitriergic modulation by curcumin for its antianxiety-like activity in mice

In the present study, effect of curcumin (10 and 20 mg/kg), an active constituent of Curcuma longa was evaluated for its antianxiety-like activity in mice subjected to immobilization-induced restraint stress for 6 h. The effect on anxiety was assessed by employing elevated plus maze, open field test, light/dark test and social interaction test. Only the higher dose (20 mg/kg, i.p.) of curcumin produced significant antianxiety-like effect in stressed mice. Pre-treatment with aminoguanidine (50 mg/kg; i.p.), an inducible nitric oxide synthase inhibitor significantly enhanced the anxiolytic-like effect of curcumin in stressed mice as compared to curcumin and aminoguanidine per se in stressed mice. Pretreatment with 7-nitroindazole (20 mg/kg), a neuronal nitric oxide synthase inhibitor did not significantly affect the antianxiety-like response of curcumin in stressed mice as compared to curcumin per se. Restraint stress significantly increased plasma nitrite levels in mice. Curcumin (20 mg/kg, i.p.) and aminoguanidine significantly decreased plasma nitrite levels in stressed mice. The combination of aminoguanidine and curcumin significantly decreased the plasma nitrite levels as compared to curcumin and aminoguanidine per se in stressed mice. Curcumin and aminoguanidine did not produce any significant change in brain GABA contents of the animals. Diazepam (2 mg/kg) produced significant anxiolytic-like effect only in unstressed mice, but could not exert significant anxiolysis in stressed mice. However, diazepam significantly increased GABA contents in both unstressed and stressed mice as compared to respective control groups. These findings suggest the possible involvement of only inducible NOS and not neuronal NOS in antianxiety-like effect of curcumin.

Research highlights
► Significant antianxiety-like effect by curcumin (20 mg/kg, i.p.) in stressed mice.
► No significant change in brain GABA contents by curcumin.
► Involvement of only iNOS and not nNOS in antianxiety-like effect of curcumin.
► Significant anxiolytic-like effect by diazepam (2 mg/kg) in unstressed mice only.
► Significant increase in brain GABA by diazepam in unstressed and stressed mice.