Neuroprotective and antidepressant-like effects of melatonin in a rotenone-induced Parkinson’s disease model in rats

• Intraperitoneal rotenone exposure produced nigral dopaminergic degeneration.
• Intraperitoneal rotenone exposure generated depressive-like behavior.
• Melatonin treatment produced antidepressant-like effect.
• Melatonin treatment exerted neuroprotective effect.

Parkinson׳s disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Systemic and intranigral exposure to rotenone in rodents reproduces many of the pathological and behavioral features of PD in humans and thus has been used as an animal model of the disease. Melatonin is a neurohormone secreted by the pineal gland, which has several important physiological functions. It has been reported to be neuroprotective in some animal models of PD. The present study investigated the effects of prolonged melatonin treatment in rats previously exposed to rotenone. The animals were intraperitoneally treated for 10 days with rotenone (2.5 mg/kg) or its vehicle. 24 h later, they were intraperitoneally treated with melatonin (10 mg/kg) or its vehicle for 28 days. One day after the last rotenone exposure, the animals exhibited hypolocomotion in the open field test, which spontaneously reversed at the last motor evaluation. We verified that prolonged melatonin treatment after dopaminergic lesion did not alter motor function but produced antidepressant-like effects in the forced swim test, prevented the rotenone-induced reduction of striatal dopamine, and partially prevented tyrosine hydroxylase immunoreactivity loss in the SNpc. Our results indicate that melatonin exerts neuroprotective and antidepressant-like effects in the rotenone model of PD.