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The present study was carried out to elucidate the beneficial effect of pioglitazone in cognitive impairment induced by bilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in substantia nigra pars compacta (SNc) in rats, a model of Parkinson's disease. MPTP-lesioned rats showed poor cognitive performance in both passive avoidance task and cued version of the Morris water maze test. This deficit in learning and memory was found to be associated with oxidative stress. Chronic administration of pioglitazone (10 and 30mg/kg, p.o., starting 5 days prior to MPTP administration and then for next 30 days) in MPTP-lesioned rats improved cognitive performance in passive avoidance task and cued version of the Morris water maze test. Furthermore, pioglitazone treatment also reduced oxidative stress (as evident by reduced malondialdehyde and increased glutathione levels). These results …