ABSTRACT Parkinson disease (PD) is a neurodegenerative disorder that affects movement due to the progressive degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNc). L-DOPA is the most common drug for the treatment of PD because of its clinical efficacy. However, long-term treatment frequently induces the development of L-DOPA-induced dyskinesias (LID). Several evidences suggest that L-DOPA can increase the pre-existing condition of oxidative stress and for this reason in the present study we combine the L-DOPA-treatment with melatonin, considering the latter as an antioxidant. Hence, we conducted the present study to determine the ability of melatonin alone or melatonin in combination with L-DOPA to protect nigrostriatal dopaminergic loss and motor impairment induced by 6-OHDA (6-hydroxydopamine) in a rat model of PD, comparing the results with L-DOPA-alone treated rats. 36 Wistar rats were stereotactically injected with either 6-OHDA or vehicle. 48 hrs after the lesion, circling behavior was evaluated. Two days after the evaluation, the rats were treated with L-DOPA (7.5 mg/kg; n = 5), or co-administrated with L-DOPA/melatonin (10 mg/kg; n = 5) orally for 6 months, and 5 lesioned rats without treatment were kept for the same time. Motor behavior was evaluated by means of the stepping ability while walking on beams and the severity of LIDs were assessed using measures of abnormal involuntary movements (AIMs). At the cellular level, the number of TH-positive immune cells and dendritic spines of the striatal medium-size spiny neurons were evaluated. Our results show that the rats with the co-administration of L-DOPA/melatonin had the best performance in the motor tasks and decreased LIDs, through the increase in the number of dopaminergic cells and the conservation of dendritic spines, which in turn imply a well-preserved synaptology of a less denervated striatum. Our results suggest that the co-administration of L-DOPA/melatonin could be a possible candidate for the treatment of PD to prevent or slow the damage caused by L-DOPA.
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