Nitric oxide involvement in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test

Abstract In the present study we evaluated the involvement of l -arginine/nitric oxide (NO)/cGMP pathway in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test (FST). Lithium, at 30 and 100 mg/kg, significantly reduced the immobility times of mice in the FST, whereas at lower doses (0.5, 5 and 10 mg/kg) had no effect on the immobility time. The NO synthase (NOS) inhibitor N G -nitro- l -arginine methyl ester ( l -NAME), at 10 and 30 mg/kg, and the selective neuronal NOS inhibitor N ω -propyl- l -arginine ( l -NPA), at 5 and 15 mg/kg, had no significant effects on the FST, whereas they significantly decreased the immobility time at 100 and 30 mg/kg, respectively. Combination of non-effective dose of lithium (10 mg/kg) with low doses of l -NAME (30 mg/kg) or l -NPA (15 mg/kg) significantly reduced the immobility times in the FST. Moreover, the guanylyl cyclase inhibitor ODQ at 50 mg/kg significantly decreased the immobility time of mice, whereas it had not significant effects on the FST at 2, 10 and 20 mg/kg. Combination of lithium (10 mg/kg) with 20 mg/kg ODQ significantly decreased the immobility times in the FST. Non-effective doses of l -arginine (750 mg/kg) or sildenafil (5 mg/kg) significantly reversed the antidepressant-like effect of 30 mg/kg lithium in the FST. Neither of the drugs had effect on the locomotor activity. These data indicate the involvement of l -arginine/NO/cGMP pathway in the antidepressant-like effect of lithium in the mouse FST and also might suggest the concurrent administration of NOS inhibitors and lithium as an appropriate strategy for treatment of depression.