Lesion of the substantia nigra, pars compacta impairs delayed alternation in a Y-maze in rats.

Adult male Wistar rats with bilateral substantia nigra, pars compacta (SNc) lesion induced by intranigral administration of 0.5 mumol 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were used as a model of early phase Parkinson's disease (PD). This treatment caused loss of dopaminergic cells in the SNc and a partial depletion of striatal dopamine. Animals trained up to 80% correct choices presented significantly worse scores after SNc lesion compared to sham-operated animals and spent almost 6 days to reach this criterion again, while sham-operated animals reached this criterion within about 2 days. When naive animals had their SNc lesioned before training, they scored worse than sham-operated animals and took 18 days to reach the 80% correct choices criterion, while sham-operated controls reached this criterion after only 10 days. These results suggest that lesion of the SNc impairs working memory in rats performing this task, in agreement with the working memory impairment in PD patients reported in clinical studies.