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

Considering 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. Mice were treated with sub-effective or effective doses of zinc chloride (ZnCl , 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 ZnCl (10 mg/kg, po) treatment. The antidepressant-like effect of ZnCl was prevented by the treatment with ZnPP and K-252a. Furthermore, sub-effective doses of CoPP and ZnCl produced a synergistic antidepressant-like effect in the TST. None of the treatments altered locomotor activity. ZnCl administration increased HO-1 immunocontents only in the prefrontal cortex. The results indicate that the antidepressant-like effect of ZnCl in the TST may depend on the induction of HO-1, and activation of TrkB receptor.