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.