Antidepressant-like effect of 7-nitroindazole in the forced swimming test in rats

Rationale: There is some strong evidence about the role of nitric oxide (NO ) as an intercellular messenger in central physiological mechanisms. NO is synthesized from L-arginine by nitric oxide synthase (NOS), as a response t o activation of N-methyl-D-aspartate (NMDA) receptors by excitatory amino a cids. NMDA receptor antagonists also produce antidepressant-like actions in preclinical models. Objective: In the present study, the involvement of NO in the mechanism of depression was investigated. 7-Nitroindazole (7-NI) (1 5, 30, 60, 90 mg/kg IF), a selective inhibitor of neuronal NOS was examined . Methods: The Porsolt forced swimming test (FST) has been used as a test f or screening new antidepressant agents. Results: 7-NI dose-dependently decr eased the immobility time in FST, but produced no significant change in loc omotor activity in naive rats. Neither L-arginine, nor D-arginine (100 mg/k g) affected the immobility time in the FST or revealed any effect on locomo tion. L-Arginine but not D-arginine, given 10 min before 7-NI, reversed the 7-NI-induced effect on immobility time. Conclusion: Our findings suggest t hat NO might be an important modulator of depression in rats.