Ventral striatal D-3 receptors and Parkinson's disease

Antiparkinsonian drugs are thought to act largely through the D2 receptor f amily that includes the D-2 and D-3 receptors. D-2 and D-3 receptors exhibi t both complementary and overlapping expression at the macro and cellular l evel. The D-3 receptor appears to be a primary target of the mesolimbic dop amine system, is highly enriched in expression within the "limbic" striato- pallidal-thalamic loop, and is recognized as bring regulated by dopaminergi c activity in distinctly different ways from the D-2 receptor. In Parkinson 's Disease it has been determined that loss of dopaminergic innervation res ults in elevation of the D-2 receptor but reduced levels of the D-3 recepto r. In many late-stage Parkinson's Disease patients then is a loss of antipa rkinsonian response to L-dopa and other antiparkinsonian drugs that is ofte n correlated with clinical signs for dementia. We have determined that the reduction of D-3 receptor, and not that of the D-2 receptor, is associated with the loss of response to L-dopa and other antiparkinsonian drugs. The r eduction of D-3 receptor is also related to the presence of dementia. An el evation of D-3 receptors was evident in those Parkinson's Disease cases wit h continued good response to L-dopa. Thus, we believe that reduced D-3 rece ptor number is correlated with certain subgroups of Parkinson's Disease and may also be related to a further diminishment in the mesolimbic DA system. (C) 2001 Elsevier Science Ltd. All rights reserved.