Behavioral Effects of Renin-Angiotensin System Modulators in a Rotenone-Induced Model of Parkinson’s Disease in Wistar Albino Rats

Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor dysfunction resulting from dopaminergic neuronal loss. Emerging evidence suggests a role of the renin-angiotensin system (RAS) in neurodegeneration, making it a potential therapeutic target. The present study aimed to evaluate the behavioral effects of captopril, perindopril, and losartan on motor, behavioral, and anxiety parameters in a rotenone-induced model of Parkinson’s disease in Wistar albino rats. Materials and methods: An experimental in vivo study was conducted using a rotenone-induced PD model in Wistar albino rats (n = 6 per group). Animals were divided into six groups: vehicle control, rotenone control, standard treatment group (levodopa + benserazide), and treatment groups receiving captopril, perindopril, or losartan along with rotenone. Neurobehavioral assessments included locomotor activity, rotarod performance, wire-hanging test, hole board test, forced swim test, and elevated plus maze. Data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test. Results: Rotenone administration significantly impaired motor and behavioral parameters, with reduced locomotor activity (18.67 ± 4.11 vs 174.33 ± 25.01 counts/10 min), rotarod performance (10.17 ± 1.19 vs 118.17 ± 1.83 sec), and wire-hanging performance (8.83 ± 1.80 vs 116.33 ± 3.67 sec), along with increased immobility-related and anxiety-like behavioral changes (P < 0.001). Treatment with captopril, perindopril, and losartan significantly improved motor performance and behavioral outcomes, with locomotor activity ranging from 141.83 to 154.50 counts/10 min and rotarod performance from 108.67 to 114.17 sec. Significant reductions in immobility time and improvements in exploratory and anxiety-related parameters were also observed (P < 0.001). Conclusion: RAS modulation using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers demonstrated significant improvement in motor and behavioral parameters in a rotenone-induced PD model. These findings suggest the potential therapeutic utility of these agents in mitigating both motor and non-motor manifestations associated with PD. However, further biochemical, histopathological, mechanistic, and clinical investigations are required to establish their potential neuroprotective role.