Tissue alterations were evaluated through Nissl staining, tyrosine hydroxylase immunohistochemistry, and Golgi-Cox staining, whereas oxidative stress levels were determined by analyzing malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (TAC) markers.<h4>Results</h4>Our results demonstrate that 10 mg/kg of nortriptyline in combination with L-DOPA and benserazide significantly improved motor activity and reduced the anxiety- and depression-like behaviors of PD. This evidence concerns the gene SOD1 and major depressive disorder.