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Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive dopaminergic dysfunction in the nigrostriatal pathway, as well as alterations in other monoamines systems. Research indicates that the use of β-adrenergic agonist and antagonists influences the risk of PD. This study evaluated the effects of salbutamol and propranolol on motor and neurochemical parameters in a progressive model of parkinsonism induced by reserpine (RES). Male Wistar rats were chronically treated with 12 subcutaneous injections of RES (0,1 mg/Kg) given every other day for 24 days. From the 16 th day onwards, the animals were daily treated with salbutamol (5 mg/Kg) or propranolol (20 mg/Kg) intraperitoneally for 8 days. Salbutamol reduced the motor deficit caused by RES in the catalepsy test, while propranolol reduced the damages caused by RES in the vacuous chewing movements evaluation. In immunohistochemical analysis both salbutamol and propranolol prevented dopaminergic damage in the substantia nigra pars compacta (SNpc), ventral tegmental area (VTA), striatum and noradrenergic damage in locus coeruleus (LC). In addition, salbutamol and propranolol prevented the increase in α-synuclein immunoreactivity caused by RES in the substantia nigra pars reticulata (SNr), striatum, prefrontal cortex (mPFC) and hippocampus. These data show that salbutamol and propranolol promote neuroprotective effects against reserpine-induced parkinsonism. However, further studies are needed to understand the mechanisms involved in β-adrenoceptors role in PD development., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2025. Published by Elsevier Ltd.)