Long‐term changes of striatal dopamine D2 Receptors in patients with Parkinson's disease: A study with positron emission tomography and [11C]Raclopride
Identifieur interne : 005319 ( Main/Exploration ); précédent : 005318; suivant : 005320Long‐term changes of striatal dopamine D2 Receptors in patients with Parkinson's disease: A study with positron emission tomography and [11C]Raclopride
Auteurs : Angelo Antonini [Suisse] ; Johannes Schwarz [Suisse] ; Wolfgang H. Oertel [Suisse] ; Oliver Pogarell [Suisse] ; Leenders [Suisse, Allemagne]Source :
- Movement Disorders [ 0885-3185 ] ; 1997-01.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Aged, Antiparkinson Agents (therapeutic use), Caudate Nucleus (drug effects), Caudate Nucleus (physiopathology), Caudate Nucleus (radionuclide imaging), Corpus Striatum (drug effects), Corpus Striatum (physiopathology), Corpus Striatum (radionuclide imaging), Corpus striatum, D2 Dopamine receptor, Dopamine Agonists (therapeutic use), Dopamine Antagonists (pharmacokinetics), Dopamine D2 receptors, Dopamine antagonist, Drug Therapy, Combination, Emission tomography, Exploration, Female, Follow-Up Studies, Human, Humans, Levodopa (therapeutic use), Long term, Longitudinal Studies, Male, Middle Aged, Neural Pathways (drug effects), Neural Pathways (physiopathology), Neural Pathways (radionuclide imaging), Neuroleptic, Parkinson Disease (drug therapy), Parkinson Disease (physiopathology), Parkinson Disease (radionuclide imaging), Parkinson disease, Parkinson's disease, Positron, Positron emission tomography, Psychotropic, Putamen (drug effects), Putamen (physiopathology), Putamen (radionuclide imaging), Raclopride, Receptors, Dopamine D2 (drug effects), Receptors, Dopamine D2 (physiology), Salicylamides (pharmacokinetics), Substantia Nigra (drug effects), Substantia Nigra (physiopathology), Substantia Nigra (radionuclide imaging), Tomography, Emission-Computed, [11C]Raclopride.
- MESH :
- chemical , drug effects : Receptors, Dopamine D2.
- chemical , pharmacokinetics : Dopamine Antagonists, Salicylamides.
- chemical , physiology : Receptors, Dopamine D2.
- chemical , therapeutic use : Antiparkinson Agents, Dopamine Agonists, Levodopa.
- drug effects : Caudate Nucleus, Corpus Striatum, Neural Pathways, Putamen, Substantia Nigra.
- drug therapy : Parkinson Disease.
- physiopathology : Caudate Nucleus, Corpus Striatum, Neural Pathways, Parkinson Disease, Putamen, Substantia Nigra.
- radionuclide imaging : Caudate Nucleus, Corpus Striatum, Neural Pathways, Parkinson Disease, Putamen, Substantia Nigra.
- Aged, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Raclopride, Tomography, Emission-Computed.
Abstract
We used [11C]raclopride (RACLO) and positron emission tomography (PET) to study longitudinally striatal dopamine D2 receptor binding in nine patients with Parkinson's disease (PD) at an early drug‐naive stage and 3–5 years later, when motor fluctuations had appeared in seven of them. Patients were treated with a combination of levodopa and dopamine agonists. Data were compared with 10 healthy controls in the same age range. Initially, patients with PD showed a significant increase of RACLO uptake in the putamen compared with controls (p < 0.04). The caudate nucleus revealed values in the normal range. After 3–5 years, RACLO binding was significantly reduced in the putamen (p < 0.03) and caudate nucleus (p < 0.03) compared with baseline. Values were now in the control range in the putamen and reduced in the caudate nucleus (p < 0.05). The clinical score at “off” had significantly worsened (p < 0.0005) compared with the first PET scan. The nine PD patients reported here had already been investigated 3–4 months after therapy began and at that time did not show a reduction of the initially increased RACLO binding capacity (data published previously). These results indicate long‐term downregulation of striatal dopamine D2 receptor binding in PD. Receptor changes in the striatum of patients with PD may be induced by chronic dopaminergic therapy or occur independently of treatment, as a result of structural adaptation of the postsynaptic dopaminergic system to the progressive decline of nigrostriatal neurons.
Url:
DOI: 10.1002/mds.870120107
Affiliations:
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Le document en format XML
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<term>Antiparkinson Agents (therapeutic use)</term>
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<term>Caudate Nucleus (physiopathology)</term>
<term>Caudate Nucleus (radionuclide imaging)</term>
<term>Corpus Striatum (drug effects)</term>
<term>Corpus Striatum (physiopathology)</term>
<term>Corpus Striatum (radionuclide imaging)</term>
<term>Corpus striatum</term>
<term>D2 Dopamine receptor</term>
<term>Dopamine Agonists (therapeutic use)</term>
<term>Dopamine Antagonists (pharmacokinetics)</term>
<term>Dopamine D2 receptors</term>
<term>Dopamine antagonist</term>
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<term>Emission tomography</term>
<term>Exploration</term>
<term>Female</term>
<term>Follow-Up Studies</term>
<term>Human</term>
<term>Humans</term>
<term>Levodopa (therapeutic use)</term>
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<term>Longitudinal Studies</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Neural Pathways (drug effects)</term>
<term>Neural Pathways (physiopathology)</term>
<term>Neural Pathways (radionuclide imaging)</term>
<term>Neuroleptic</term>
<term>Parkinson Disease (drug therapy)</term>
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<term>Parkinson Disease (radionuclide imaging)</term>
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<front><div type="abstract" xml:lang="en">We used [11C]raclopride (RACLO) and positron emission tomography (PET) to study longitudinally striatal dopamine D2 receptor binding in nine patients with Parkinson's disease (PD) at an early drug‐naive stage and 3–5 years later, when motor fluctuations had appeared in seven of them. Patients were treated with a combination of levodopa and dopamine agonists. Data were compared with 10 healthy controls in the same age range. Initially, patients with PD showed a significant increase of RACLO uptake in the putamen compared with controls (p < 0.04). The caudate nucleus revealed values in the normal range. After 3–5 years, RACLO binding was significantly reduced in the putamen (p < 0.03) and caudate nucleus (p < 0.03) compared with baseline. Values were now in the control range in the putamen and reduced in the caudate nucleus (p < 0.05). The clinical score at “off” had significantly worsened (p < 0.0005) compared with the first PET scan. The nine PD patients reported here had already been investigated 3–4 months after therapy began and at that time did not show a reduction of the initially increased RACLO binding capacity (data published previously). These results indicate long‐term downregulation of striatal dopamine D2 receptor binding in PD. Receptor changes in the striatum of patients with PD may be induced by chronic dopaminergic therapy or occur independently of treatment, as a result of structural adaptation of the postsynaptic dopaminergic system to the progressive decline of nigrostriatal neurons.</div>
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