**Abstract**

Parkinson disease (PD) is characterized by dopaminergic neuron loss of the substantia nigra compacta (SNc) and motor alterations. Here, we used the experimental model of inhalation of the mixture of manganese chloride (MnCl2) and manganese acetate Mn (OAc)3 for inducing PD. This model causes bilateral and progressive degeneration of the SNc dopaminergic neurons. Melatonin has antioxidant properties and it has been suggested that it contributes to the protective effect in neurodegenerative diseases. Therefore, we aimed to determine whether melatonin pretreatment protects against the Mn-induced alterations. Before Mn inhalation, three groups were trained for motor performance (1. control group, 2. Mn mixture exposed without pretreatment, and 3. melatonin-pretreated/Mn-exposed groups) for motor tests. The motor coordination was evaluated through the single-pellet reaching task and the beam-walking test. After five months, all the animals were sacrificed. Dendritic spines were counted in the striatum medium-sized spiny neurons and the number of TH-immunoreactive neurons in the SNc. Our findings show that the melatonin-pretreated animals had better motor coordination and less dendritic spines and TH immunoreactive neuron loss than the Mn-inhalation-only group. Therefore, melatonin pretreatment has a neuroprotective effect and could be considered an alternative treatment before the more severe PD symptoms appear.

**Keywords:** melatonin pretreatment, Parkinson disease, manganese inhalation, motor performance, dendritic spines, TH immunohistochemistry
