A role for nitrergic system in the antidepressant-like effects of chronic lithium treatment in the mouse forced swimming test

In the present study we evaluated the involvement of nitric oxide (NO) system in the antidepressant-like effects of chronic lithium administration in the mouse forced swimming test (FST). Administration of lithium chloride (300 mg/L in drinking water for 21 days) had no effect on the immobility of mice in the FST, whereas 600 mg/L lithium caused a significant (P < 0.001) decrease in the immobility time compared with control animals. Administration of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, daily for a week, i.p.) had no significant effect on the immobility time of either control or lithium (300 mg/L)-treated mice, whereas acute administration of non-effective dose of L-NAME (30 mg/kg, i.p.) caused a robust decrease (P < 0.01) in the immobility time of lithium (300 mg/L)-treated animals in the FST. Moreover, chronic administration of low dose of the NO precursor L-arginine (200 mg/kg, daily for a week, i.p.) prevented (P < 0.001) the antidepressant-like effects of lithium treatment (600 mg/L) in the FST. Acute treatment with L-arginine (200 mg/kg, i.p.) increased (P < 0.05) the immobility time of lithium (600 mg/L)-treated mice in the FST. Chronic lithium treatment (600 mg/L but not 300 mg/L) caused a significant (P < 0.05) decrease in the serum NOX levels in mice compared with controls. Our data suggested that the NO system could be involved in the antidepressant-like effect of chronic lithium treatment in the FST.