Neuroprotective effect of MK-801 against intra-striatal quinolinic acid induced behavioral, oxidative stress and cellular alterations in rats

Huntington's Disease (HD) is a common neurodegenerative disorder characterized by motor disturbances, subcortical dementia and psychiatric disturbances. Pathogenesis of HD revolves so far around excitatory amino acids as the primary cause of neuronal loss. However, number of recent reports suggests the involvement of excitotoxicity and oxidative damage. In the present study, first the dose of quinolinic acid that mimics the symptoms of HD was standardized and then the neuroprotective effect of MK-801 (noncompetitive NMDAr antagonist) was evaluated against intrastriatal quinolinic acid induced behavioral, oxidative stress and cellular alterations in rats. A single unilateral (ipsilateral striatum) injections of quinolinic acid (100, 200 and 300 nM) were made in to striatum. Animals were tested for motor functions using actophotometer and rotarod apparatus. Quinolinic acid (300 nM) significantly reduced the body weight and caused motor in-coordination and produced oxidative damage in the cortex and striatum as indicated by raised lipid peroxidation, nitrite concentration, depletion of superoxide dismutase, catalase and different glutathione levels. Beside, quinolinic acid (300 nM) significantly altered the mitochondrial enzymes complex levels and caused histopathological alterations in the striatum. MK-801(0.02, 0.04, 0.08 mg/kg, ip) treatment significantly improved body weight, behavioral alterations (locomotor activity and rotarod performance) and attenuated oxidative damage and mitochondrial enzymes complex dysfunction. Besides, MK-801 treatment significantly reversed histopathological alterations in striatum. The results suggest antioxidant and neuroprotective action of MK-801 against the quinolinic acid induced Huntington's like behavioral, oxidative stress and cellular alterations in rats.