RESUMEN
It has been well documented that administration of melatonin could reveal antidepressant-like effect in rodents. However, the protective effect of melatonin on stress-induced depression/anxiety and its underlying mechanism is yet to be understood. In this regard, in the current study, acute foot-shock stress (FSS) was used to evaluate the antidepressant-like effect of melatonin on neurogenic stress-induced depression in mice. Behavioral evaluation was done by using the forced swimming test (FST) and Open-field test (OFT). Melatonin, MK-801, and ketamine (NMDA receptor antagonists), and NMDA (NMDA receptor agonist) were used to elucidate any association between melatonin and NMDA pathway in behavioral despair induced by acute-FSS. Applying acute-FSS to mice significantly induced depressant-like behavior in FST without any significant impact on locomotor activity in the OFT. We observed that melatonin (dose-dependently) significantly improved the depressant-like effect of FSS, but it did not impact the locomotion in animals. Acute injection of MK-801 at sub-effective doses (0.01 mg/kg) or ketamine (0.1 mg/kg) potentiated the antidepressant-like effect of a sub-effective dose of melatonin. However, the sub-effective dose of NMDA (30 mg/kg) abolished the protective effect of melatonin on the behavioral profile of stressed animals. Our results could reflect the antidepressant-like effect of melatonin on neurogenic stress-induced depressive behaviors in mice. Also, our results showed that NMDA receptors could be involved in the antidepressant-like effect of melatonin.
RESUMEN
Since the inflammation and oxidative stress is the main pathophysiological pathway of neural damage in spinal cord injury (SCI), we tried to evaluate the role of ivermectin (IVM) combined with multi-walled carbon nanotube (MWCNT) in the treatment settings of SCI and its underlying mechanism. Wistar rats with T9 vertebra laminectomy in five groups of: sham-operated, vehicle, IVM (0.1 mg/kg), IVM-MWCNT (0.1 mg/kg), and minocycline (90 mg/kg) were used. We evaluated the locomotor scaling and other behavioral tests for neuropathic pain. Also, tissue samples were obtained to evaluate the expression of M1 and M2 macrophage marker, concentration of TNF-α, IL-1ß, and IL-1, and oxidative stress level to assess neuroinflammatory changes. Both IVM and IVM-MWCNT after induction of SCI significantly enhanced the experimental tasks' outcomes, including locomotion and neuropathic tests. Also, decreasing in pro-inflammatory cytokines including TNF-α, IL-1ß, and IL-1 in the spinal cord and dorsal root ganglion tissues was also notable in both IVM and IVM-MWCNT-treated groups 28 days after induction of SCI in compared to the vehicle-treated SCI group. Both IVM and IVM-MWCNT significantly decreased oxidative stress, induced by SCI, based on the results of ROS and NADPH activity. IVM-MWCNT-treated animals indicated better outcome in every previous experiment in comparison to IVM-treated animals. The effectiveness of IVM-MWCNT was similar to minocycline treatment in all experimental task (as positive control group). IVM-MWCNT might be a novel treatment in spinal cord injury, which could act through decreasing the oxidative stress and increase the polarization of M1 in comparison to M2 macrophages.