Bio-metal chromium(III) is a crucial microelement for the proper functioning of living organisms. Previous preclinical and clinical studies reported its potential antidepressant properties. The aim of the present study was to examine the effect of antidepressants and noradrenergic and dopaminergic receptor antagonists on chromium chloride (CrCl₃) activity in the forced swim test (FST) in mice and rats. Imipramine (5 mg/kg), fluoxetine (5 mg/kg) and reboxetine (5 mg/kg) but not bupropion (1 mg/kg), administered jointly with CrCl₃ at a dose of 6 mg/kg, reduced the immobility time in the FST in mice. The reduction of the immobility time induced by the active dose (12 mg/kg) of CrCl₃ was completely abolished by propranolol (2 mg/kg, β-adrenoceptor antagonist), SCH 23390 (0.5 mg/kg, a dopamine D₁ receptor antagonist), and partially by prazosin (1 mg/kg, an α₁-adrenoceptor antagonist), yohimbine (1 mg/kg, an α₂-adrenoceptor antagonist) and sulpiryd (50 mg/kg, a dopamine D₂/D₃ receptor antagonist) administration. The locomotor activity was significantly reduced by CrCl₃ + reboxetine treatment, which did not influence the reboxetine enhancement of the antidepressant-like effect of CrCl₃ in the FST. Moreover, CrCl₃ at a dose of 32 mg/kg (although not at 12 mg/kg) significantly reduced the immobility and enhanced the climbing (but not swimming) time in the FST in rats, which indicates the involvement of the noradrenergic pathway in this effect. The present study indicates that the antidepressant-like activity of chromium in the FST is dependent (although to a different extent) on the noradrenergic, dopaminergic and serotonin systems.

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