Antidepressant-Related Signaling Pathways of Zinc Oxide Nanoparticles in a Mouse Model of Postpartum Depression

Postpartum depression (PPD) constitutes a serious mental health concern linked to behavioral disturbances. Zinc exerts a significant influence on mood states. This novel study revealed the antidepressant-like action of zinc oxide nanoparticles (ZnO NPs) and their underlying mechanisms in the PPD model through the forced swimming test (FST), emphasizing their therapeutic potential for maternal mental health. PPD was induced in female mice via intraperitoneal injection of progesterone (5 mg/kg) for 5 days, followed by 3 days withdrawal period. The depressed mice received ZnO NPs (5, 10, and 20 mg/kg) 30 min before the FST. Moreover, L-arginine (NO precursor, 750 mg/kg), L-NAME (non-specific NOS inhibitor, 10 mg/kg), WAY100635 (selective 5-HT_1A receptor antagonist, 0.1 mg/kg), caffeine (non-selective adenosine receptor antagonist, 3 mg/kg), adenosine (non-selective adenosine receptor agonist, 0.1 mg/kg), NMDA (NMDA receptor agonist, 75 mg/kg), MK-801 (NMDA receptor antagonist, 0.05 mg/kg) were used to ascertain the neural pathways implicated in the antidepressant-like response of ZnO NPs. ZnO NPs exhibited a significant and dose-dependent decrease in immobility time. Prior administration of L-arginine, WAY100635, caffeine, and NMDA suppressed the anti-immobility effect of the maximal effective dose of ZnO NPs. Pre-treatment with L-NAME, adenosine, and MK-801 amplified the decrease in immobility duration provoked by a sub-effective dose of ZnO NPs. These findings suggest that the antidepressant-like action of ZnO NPs is likely mediated through nitrergic, serotonergic, adenosinergic, and glutamatergic pathways.