Loss of response to levodopa in Parkinson's disease and co-occurrence with dementia: Role of D3 and not D2 receptors

J. N. Joyce, H. L. Ryoo, T. B. Beach, J. N. Caviness, Mark Stacy, E. V. Gurevich, Mark Reiser, C. H. Adler

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Previous data suggest a relationship between the loss of response to levodopa in Parkinson's disease (PD) patients with the co-occurrence of dementia, but the role of alterations in the dopamine system has not been explored. We measured the extent of striatal DA loss and changes in striatal DA D2 and D3 receptors in postmortem striatum of PD patients who historically had or had not lost their clinical response to dopaminergic drugs and/or had an additional diagnosis of dementia. Clinical evaluation and retrospective chart reviews for PD and dementia, and neuropathological diagnoses were obtained. All PD cases (±dementia), regardless of response to dopaminergic drugs, exhibited a significant and similar degree and pattern of loss of tyrosine hydroxylase immunocytochemistry and DA transporter binding in striatum, and loss of tyrosine hydroxylase-immunoreactive neurons and brain-derived neurotrophic-immunoreactive neurons from the ventral midbrain. D2 receptor concentrations were modestly elevated in the rostral striatum of all the PD cases (±dementia), whether or not they continued to respond to dopaminergic drugs. In contrast, loss of D3 receptor concentration correlated with loss of response to dopaminergic drugs, independent of the presence or absence of dementia. A maintained response to dopaminergic drugs correlated with an elevation of D3 receptors. Dementia with PD was highly correlated with a loss of response to dopaminergic drugs, and was also correlated with reduced D3 receptors. The alterations in D3 receptor concentrations were greatest in the nucleus accumbens, caudal striatum, and globus pallidus. Thus, loss of dopamine D3 receptors may be a more important contributing factor to a loss of response to dopaminergic drugs than changes in the D2 receptor.

Original languageEnglish (US)
Pages (from-to)138-152
Number of pages15
JournalBrain Research
Volume955
Issue number1-2
DOIs
StatePublished - Nov 15 2002

Keywords

  • Dopamine D receptor
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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    Joyce, J. N., Ryoo, H. L., Beach, T. B., Caviness, J. N., Stacy, M., Gurevich, E. V., Reiser, M., & Adler, C. H. (2002). Loss of response to levodopa in Parkinson's disease and co-occurrence with dementia: Role of D3 and not D2 receptors. Brain Research, 955(1-2), 138-152. https://doi.org/10.1016/S0006-8993(02)03396-6