10.22376/ijpbs.2019.10.1.p1-12 Volume 11 Issue 4 2020 (October-December) One of the major lacunae in the preclinical drug discovery is the lack of an animal model which recapitulates the pathophysiology as well as the behavioural symptoms of clinical Parkinson's disease (PD). The aim of the present study was to compare the effects of unilateral and bilateral stereotaxic injection of rotenone to develop an optimised PD model. In the present study, 20 adult male Sprague Dawley rats (200-250 g) were assigned to four groups with 5 animals in each. These groups comprised of Sham, vehicle control, unilateral and bilateral rotenone (12 µg/µl) injection in Substantia nigra (SN). The behavioural parameters concerning the grip strength and neuromuscular coordination was examined by means of wire hang test. Then, we analysed biochemical parameters involving mitochondrial complex I inhibition and oxidative stress (Reduced GSH, Superoxide dismutase). The results were correlated with the histopathological assessment determining the neuronal death. Both unilateral and bilateral administration resulted in a decrease in latency to fall with the loss in grip being more severe in the bilateral group. The mitochondrial complex I inhibition due to rotenone resulted in the significant increase in oxidative stress. The histopathological analysis revealed severe neuronal apoptosis in substantia nigra suggesting neurodegeneration, which was more evident in bilateral groups. Both unilateral and bilateral administration result in induction of the symptoms and pathophysiological changes. However, bilateral administration proved to be a better delivery strategy for the development of PD animal models. Vaibhavi Peshattiwar and Sadhana Sathaye Parkinson’s Disease, Rotenone, bilateral stereotaxy, mitochondrial complex I, neurodegeneration. 54-60