Ventral striatal D₃ receptors and Parkinson's Disease

Antiparkinsonian drugs are thought to act largely through the D2 receptor family that includes the D₂ and D₃ receptors. D₂ and D₃ receptors exhibit both complementary and overlapping expression at the macro and cellular level. The D₃ receptor appears to be a primary target of the mesolimbic dopamine system, is highly enriched in expression within the 'limbic' striato-pallidal-thalamic loop, and is recognized as being regulated by dopaminergic activity in distinctly different ways from the D₂ receptor. In Parkinson's Disease it has been determined that loss of dopaminergic innervation results in elevation of the D₂ receptor but reduced levels of the D₃ receptor. In many late-stage Parkinson's Disease patients there is a loss of antiparkinsonian response to L-dopa and other antiparkinsonian drugs that is often correlated with clinical signs for dementia. We have determined that the reduction of D₃ receptor, and not that of the D₂ receptor, is associated with the loss of response to L-dopa and other antiparkinsonian drugs. The reduction of D₃ receptor is also related to the presence of dementia. An elevation of D₃ receptors was evident in those Parkinson's Disease cases with continued good response to L-dopa. Thus, we believe that reduced D₃ receptor number is correlated with certain subgroups of Parkinson's Disease and may also be related to a further diminishment in the mesolimbic DA system.