Intrapallidal dopamine restores motor deficits induced by 6-hydroxydopamine in the rat

To explore whether dopamine deficits in the globus pallidus have a role in generating the motor symptoms of Parkinson's disease, we examined the effec ts of selective intrapallidal administration of dopamine or its antagonists in rats unilaterally lesioned with 6-hydroxydopamine into the medial foreb rain bundle. Either the turning behavior induced by apomorphine or the defi cit in the performance of a skilled forelimb-reaching task was used as assa y for drug action. Microinjection of either the D2 receptor antagonist, sul piride, or the D1 receptor antagonist, SCH-23390, into the dopamine-denerva ted pallidum significantly reduced apomorphine induced turning. In animals trained to perform a skilled forelimb-reaching task, 6-OHDA lesions caused a marked motor deficit in the contralateral forelimb. Intrapallidal dopamin e applied either intermittently or continuously, restored up to 50% of the motor performance. Continuous application promoted a motor recovery that ou tlasted dopamine administration. These results show that lack of dopamine i n the GP plays an important role in generating the motor symptoms caused by lesion of dopaminergic pathways. Moreover, motor recovery was produced by selectively injecting dopamine into the globus pallidus.