Behavioural pharmacologyElevated level of nitric oxide mediates the anti-depressant effect of rubidium chloride in mice

- Rubidium chloride decreased immobility in forced-swimming and tail-suspension tests.
- Nitric oxide synthase inhibitors inhibit the anti-immobility effect of rubidium chloride.
- Nitric oxide precursor exerts synergistic effect with rubidium chloride in the tests.
- Rubidium chloride enhanced the NOx level in serum and hippocampus of mice.
- Rubidium chloride exerts antidepressant-like effect through nitric oxide elevation.

Rubidium has been used to treat psychiatric conditions including depression. We examined the antidepressant activity of rubidium chloride (RbCl) in male mice and the possible interference of nitric oxide (NO) in this effect. Mouse forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant-like effect of RbCl. These drugs were used in this study: NG-l-arginine methyl ester (l-NAME), a non-selective nitric oxide synthase (NOS) inhibitor, 7-Nitroindazole and aminoguanidine, selective neuronal and inducible NOS inhibitors, respectively, and l-arginine, an NO precursor. We studied the changes of serum and hippocampus nitrite level after different treatments. RbCl (30 mg/kg), when administered 60 min before the tests, significantly reduced the immobility time. Non-effective doses of l-NAME (10 mg/kg) and aminoguanidine (50 mg/kg), co-administered with the effective dose of RbCl (30 mg/kg), reversed the anti-immobility effect of RbCl, while 7-NI (25 mg/kg) could not prevent the diminishing effect of RbCl on immobility time. Moreover, co-administration of non-effective doses of l-arginine (750 mg/kg) and RbCl (10 mg/kg) decreased the immobility time. None of the mentioned treatments altered the locomotor activity of mice in open-field test. Nitrite level was significantly increased in serum and hippocampus of animals after RbCl (30 mg/kg) administration and this nitrite level elevation was reversed by non-effective dose of l-NAME and aminoguanidine, but not 7-NI. Our data for the first time reveal the role of NO pathway in the antidepressant-like activity of RbCl, concluding that this effect results from elevation of NO through involvement of iNOS in mice.