Original articleEvidence for the involvement of heme oxygenase-1 in the antidepressant-like effect of zinc

- HO-1 inhibitor prevents the anti-immobility effect of ZnCl2 in TST.
- HO-1 inducer combined with ZnCl2 produces an antidepressant-like effect in TST.
- TrkB receptor antagonist prevents the anti-immobility effect of ZnCl2 in TST.
- ZnCl2 administered acutely increases HO-1 immunocontent in prefrontal cortex.
- ZnCl2 effect in TST may be dependent on both HO-1 and TrkB receptor activation.

BackgroundConsidering that heme oxygenase-1 (HO-1) and the brain-derived neurotrophic factor (BDNF)-mediated pathway are involved in the pathophysiology of depression and that zinc has been shown to exert beneficial effects in the management of depression, this study investigated the influence of these targets on the antidepressant-like effect of zinc.MethodsMice were treated with sub-effective or effective doses of zinc chloride (ZnCl2, 10 mg/kg, po), and 45 min later, they received intracerebroventricular (icv) injections of sub-effective doses of either zinc protoporphyrin IX (ZnPP, 10 μg/mouse, HO-1 inhibitor), cobalt protoporphyrin IX (CoPP, 0.01 μg/mouse, HO-1 inducer) or K-252a (1 μg/mouse, TrkB receptor antagonist). Immobility time and locomotor activity were evaluated through the tail suspension test (TST) and open-field test (OFT), respectively. HO-1 immunocontents were evaluated in the prefrontal cortex and hippocampus 60 min after ZnCl2 (10 mg/kg, po) treatment.ResultsThe antidepressant-like effect of ZnCl2 was prevented by the treatment with ZnPP and K-252a. Furthermore, sub-effective doses of CoPP and ZnCl2 produced a synergistic antidepressant-like effect in the TST. None of the treatments altered locomotor activity. ZnCl2 administration increased HO-1 immunocontents only in the prefrontal cortex.ConclusionsThe results indicate that the antidepressant-like effect of ZnCl2 in the TST may depend on the induction of HO-1, and activation of TrkB receptor.