Motor effects and mapping of cerebral alterations in animal models of Parkinson's and Huntington's diseases

Changes in stimulant-induced behavioral effects and subcortical c-Fos expre ssion were compared between rodent models of Parkinson's disease (PD) and H untington's disease (HD). Rats received either a unilateral 6-hydroxydopami ne (6-OHDA)-induced lesion of the nigrostriatal dopamine pathway (PD model) or a unilateral infusion of antisense oligodeoxynucleotides targeting c-fo s into the striatum (HD model). Dopamine-lesioned animals received intraper itoneal injections of either d-amphetamine (6-OHDAamp group) or apomorphine (B-OHDAapo group), whereas all animals that received antisense infusions r eceived d-amphetamine (ASF group). All groups exhibited robust circling beh avior upon stimulant challenge. Changes in subcortical activation, as asses sed by the induction of Fos-Like immunoreactivity (Fos-LI), were examined i n several brain regions. The 6-OHDAamp and ASF groups exhibited robust, ips iversive circling behavior, with similar changes in Fos-LI in the striatum, entopeduncular nucleus, superior colliculus, and ventromedial thalamus. Th e 6-OHDAapo group exhibited contraversive rotation and had reciprocal patte rns of Fos-LI in these regions. Despite exhibiting the same direction of ro tation, the 6-OHDAamp and ASF groups had markedly different patterns of Fos -LI in the globus pallidus and the pontine reticular formation. These resul ts suggest that the globus pallidus may undergo distinct alterations in PD and IID and that the pontine reticular formation is particularly susceptibl e to changes in mesencephalic dopamine sources. (C) 1999 Wiley-Liss, Inc.