Comparison of bilaterally 6-OHDA- and MPTP-lesioned rats as models of the early phase of Parkinson's disease: histological, neurochemical, motor and memory alterations.

This study compares histological, neurochemical, behavioral, motor and cognitive alterations as well as mortality of two models of Parkinson's disease in which 100 microg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6 microg 6-hydroxydopamine (6-OHDA) was bilaterally infused into the central region of the substantia nigra, compact part, of adult male Wistar rats. Both neurotoxins caused a significant loss of nigral tyrosine hydroxylase-immunostained cells and striatal dopamine depletion, but 6-OHDA caused more widespread and intense cell loss, more intense body weight loss and more mortality than MPTP. Both 6-OHDA- and MPTP-lesioned rats presented similar deficits in performing a working memory and a cued version of the Morris water maze task and few exploratory/motor alterations in the open field and catalepsy tests. However, rats presented a significant and transitory increase in locomotor activity after the MPTP lesion and a hypolocomotor behavior tended to be present after the 6-OHDA lesion. The picture of mild motor effects and robust impairment of habit learning and spatial working memory observed in MPTP-lesioned rats models the early phase of Parkinson's disease.