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

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 D(2) and D(3) 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. D(2) 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 D(3) 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 D(3) receptors. Dementia with PD was highly correlated with a loss of response to dopaminergic drugs, and was also correlated with reduced D(3) receptors. The alterations in D(3) receptor concentrations were greatest in the nucleus accumbens, caudal striatum, and globus pallidus. Thus, loss of dopamine D(3) receptors may be a more important contributing factor to a loss of response to dopaminergic drugs than changes in the D(2) receptor.

journal_name

Brain Res

journal_title

Brain research

authors

Joyce JN,Ryoo HL,Beach TB,Caviness JN,Stacy M,Gurevich EV,Reiser M,Adler CH

doi

10.1016/s0006-8993(02)03396-6

subject

Has Abstract

pub_date

2002-11-15 00:00:00

pages

138-52

issue

1-2

eissn

0006-8993

issn

1872-6240

pii

S0006899302033966

journal_volume

955

pub_type

杂志文章

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