Unpredictable mild stress accelerates the emergence of motor deficits in a rat model of progressive parkinsonism

Parkinson’s disease (PD) is a multifactorial condition associated with genetic and environmental factors. In recent years, the role of chronic psychophysiological stress as a predisposing factor for PD is gaining increasing attention. Clinical and experimental evidence indicates that chronic stress exerts adverse effects on the brain. Nevertheless, the potential role of chronic stress in the predisposition to PD remains poorly understood. This study aimed to investigate the effects of exposure to a chronic unpredictable mild stress (UMS) protocol on the onset of parkinsonism in Wistar rats repeatedly treated with a low dose of reserpine. Wistar rats were either exposed to UMS for 1 week or not exposed (control group). Then, the animals were repeatedly treated with a low dose of reserpine or vehicle every other day for 20 days. Behavioral motor evaluations were conducted using catalepsy and open field tests. Moreover, plasma corticosterone (CORT) levels and lipid peroxidation were evaluated. As expected, the UMS protocol increased plasma CORT levels, and reserpine treatment led to a progressive enhancement of cataleptic behavior. Animals exposed to UMS and treated with reserpine exhibited motor alteration earlier during the protocol. No differences were observed in oxidative stress between experimental and control groups, as evaluated through lipid peroxidation assay. Our results showed that chronic mild stress accelerated the onset of motor deficits in reserpine-treated animals.