Melatonin modulates copper-induced anxiety-like, depression-like and memory impairments by acting on hippocampal oxidative stress in rat

Abstract

Copper (Cu) is a heavy metal with the ability to induce, at high levels, neurobehavioral alterations, and oxidative stress (OS). On the other hand, melatonin (Mel) is a neurohormone that protects neurons from OS and has a modulatory effect on several behavioral processes. The present experiment was aimed to examine the effect of Mel treatment on Cu-induced anxiety-like, depression-like behaviors, memory impairment, and OS in hippocampus. Herein, adult Wistar rats of both genders received daily Mel (4 mg/kg) thirty minutes before CuCl₂ (1 mg/kg), by intraperitoneal injections for 8 weeks. After the administration period, all rats were submitted to the behavioral tests. Thereafter, OS parameters and histology of the hippocampus were evaluated. The results demonstrate that Mel treatment attenuated Cu-induced anxiety-like and depression-like behaviors, and it improved memory deficits Cu-treated rats. Furthermore, Mel attenuated Cu-provoked OS by reducing lipid peroxidation (LPO) and nitric oxide (NO) levels and enhancing superoxide dismutase (SOD) and catalase (CAT) activities in the hippocampus. The histopathological analysis also supported these results. In conclusion, these findings show that Mel treatment exerted neuroprotective effects against Cu-induced neurobehavioral changes which may be related to reduction of hippocampal OS. Besides, the effects of Cu and Mel were gender dependent, being more marked in females compared to male rats.

Keywords:

• Copper
• melatonin
• anxiety-like
• depression-like
• memory
• oxidative stress

Acknowledgements

The authors would like to express their heartfelt and deepest condolences to family and friends of Prof. Ali Ouichou, for his loss. The neuroscience family in Morocco will miss one of its significant members, and the University Ibn Tofail has lost a great academic professor, who has contributed to the growth of the neuroscience community in Morocco.

Disclosure statement

No potential conflict of interest was reported by the author(s).