Ventral striatal D3 receptors and Parkinson's Disease

J. N. Joyce, H. Ryoo, E. V. Gurevich, C. Adler, T. Beach

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)225-230
Number of pages6
JournalParkinsonism and Related Disorders
Volume7
Issue number3
DOIs
StatePublished - May 7 2001

Keywords

  • Alzheimer's Disease
  • Basal ganglia
  • Dopamine
  • Limbic system
  • Ventral tegmental area

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

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