Sprouting of the serotonergic afferents into striatum after selective lesion of the dopaminergic system by MPTP in adult mice.

Neonatal destruction of the nigrostrial dopaminergic (DA) system with 6-hydroxydopamine leads to serotonergic (5-HT) hyperinnervation of the striatum. However, it is not clear whether this occurs in adult animals. We investigated whether serotonergic sprouting occurs in adult mice subjected to bilateral lesion of the DA system by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The effects of the lesion were evaluated using a new rotarod test and immunohistochemistry. One hundred days after the last MPTP lesion, there was a clear bilateral serotonergic hyperinnervation throughout the striatum. Additionally, those mice showing the highest reductions in striatal tyrosine hydroxylase (TH) immunoreactivity and in rotarod performance showed the highest density of serotonergic innervation (116% increase). The functional consequences of this process in Parkinson's disease and secondary parkinsonism remain to be clarified.