Neuroprotective Effect of Piracetam and Vincamine in a Rat Model of Haloperidol-induced Parkinson's Disease

Abstract

To evaluate the neuroprotective effect of nootropic drugs, piracetam and vincamine, on Parkinsonʹs disease (PD) in rats, forty adult male Wistar albino rats were randomized into five equal groups: control, haloperidol-induced PD group, and PD groups orally given piracetam (300 mg/kg/day), vincamine (20 mg/kg/day) or both. Four weeks later, motor performance was assessed by stepping test. Y-maze, forced swimming and olfactory preference tests were done for cognitive and behavioral evaluation. Blood samples were collected for measuring serum glucose, calcium, creatine phosphokinase (CPK) and glial cell-derived neurotrophic factor (GDNF). Thereafter, rats were sacrificed and brains were dissected. Striatal tissue of left hemisphere was isolated and homogenized for assay of dopamine, malondialdehyde (MDA), nitrite/nitrate, reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1ß). Right hemisphere was used for histopathological examination of substantia nigra. Results: Rats of PD group showed bradykinesia, cognitive impairment, depressive-like behavior and hyposmia, reductions in serum calcium and GDNF, and in striatal dopamine, GSH, GPx and SOD, while serum glucose and CPK, and striatal MDA, nitrite/nitrate, IL-1ß and TNF-α were increased, as compared to control. Both drugs improved neurological dysfunction and biochemical parameters, as compared to PD group. The histopathological findings revealed neuro-degeneration and neuro-inflammation in PD group, that improved in treated groups. The piracetam effect was mainly anti-inflammatory, while vincamine was mainly antioxidant. Combined treatment resulted in a more potent amelioration of haloperidol-induced changes. Conclusion: Piracetam and vincamine exhibit neuroprotective activity in haloperidol-induced PD, that is more potent with their combination. Keywords