Prevention of pro-depressant effect of l-arginine in the forced swim test by NG-nitro-l-arginine and [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one]

Previous studies have shown that l-arginine, the precursor of nitric oxide, has a dual effect (antidepressant and pro-depressant) in the forced swim test. The aim of the present study was to investigate whether nitric oxide-cGMP pathway was involved in this dual effect. Porsolt swim test was conducted to resemble the symptomatology of major depressive disorder. An open field locomotor activity test was also used. l-arginine exerted a U-shape effect in the forced swim test: doses of 30, 100, 300, and 1000 mg/kg caused no alteration, statistically significant reduction, no alteration, and non-significant enhancement, respectively. Neither NG-nitro-l-arginine (NNA) nor [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one] (ODQ) at doses of 3 mg/kg was found to be effective in the forced swim test, whereas 10 mg/kg ODQ significantly reduced the immobility time. In the presence of NNA, the antidepressant and pro-depressant effects of l-arginine disappeared, however, only the pro-depressant component of l-arginine effect was prevented by ODQ (3 and 10 mg/kg). Saline, the solvent of l-arginine and NNA, and dimethyl sulfoxide (15% in saline), the solvent of ODQ, had no effect on the duration of immobility. None of the drugs or solvents used in the present study had any effect on locomotor activity over the dose range applied. The results show that l-arginine exerts its paradoxical effects by producing nitric oxide and that cGMP seems to have a role only in the pro-depressant component.