Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson's disease: implications for dyskinesias
Identifieur interne : 001612 ( Main/Exploration ); précédent : 001611; suivant : 001613Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson's disease: implications for dyskinesias
Auteurs : Rau L De La Fuente-Ferna Ndez [Canada] ; Vesna Sossi [Canada] ; Zhigao Huang [Canada] ; Sarah Furtado [Canada] ; Jian-Qiang Lu [Canada] ; Donald B. Calne [Canada] ; Thomas J. Ruth [Canada] ; A. Jon Stoessl [Canada]Source :
- Brain [ 0006-8950 ] ; 2004-12.
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Abstract
Peak-dose dyskinesias are abnormal movements that usually occur 1 h after oral administration of levodopa, and often complicate chronic treatment of Parkinson's disease. We investigated by PET with [11C]raclopride whether Parkinson's disease progression modifies the striatal changes in synaptic dopamine levels induced by levodopa administration, and whether this modification, if present, could have an impact on the emergence of dyskinesias. We found that, 1 h after oral administration of standard-release 250/25 mg of levodopa/carbidopa, levodopa-induced increases in synaptic dopamine levels (as estimated by striatal changes in [11C]raclopride binding potential) correlated positively with duration of Parkinson's disease symptoms (for the caudate nucleus, r = 0.79, P < 0.001; for the putamen, r = 0.88, P < 0.0001). Patients with peak-dose dyskinesias had larger 1-h increases in synaptic dopamine levels than stable responders, but there were no between-group differences in [11C]raclopride binding 4 h post-levodopa. The corresponding (time × group) interaction term in the repeated measures analysis of covariance was significant, even after adjusting for between-group differences in duration of Parkinson's disease symptoms (for the caudate nucleus, P = 0.030; for the putamen, P = 0.021). Our results indicate that, at the synaptic level, an identical dose of levodopa induces increasingly larger 1-h changes in dopamine levels as Parkinson's disease progresses. Large levodopa-induced increases in synaptic dopamine concentration can lead to dramatic changes in receptor occupancy, which may be responsible for the emergence of peak-dose dyskinesias in Parkinson's disease.
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DOI: 10.1093/brain/awh290
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Jon Stoessl</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Brain</title><title level="j" type="abbrev">Brain</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2004-12">2004-12</date><biblScope unit="volume">127</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="2747">2747</biblScope><biblScope unit="page" to="2754">2754</biblScope></imprint><idno type="ISSN">0006-8950</idno></series><idno type="istex">23C99363FA901D8E11FDBF9A8773E554B1046AC2</idno><idno type="DOI">10.1093/brain/awh290</idno><idno type="local">awh290</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>BP = binding potential</term><term>Caud = caudate nucleus</term><term>MCS = modified Columbia Scale</term><term>P1, P2 and P3 = rostral to caudal putamen</term><term>PET</term><term>Parkinson's disease</term><term>RAC = [11C]raclopride</term><term>ROI = region of interest</term><term>dopamine release</term><term>dyskinesias</term><term>raclopride</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Peak-dose dyskinesias are abnormal movements that usually occur 1 h after oral administration of levodopa, and often complicate chronic treatment of Parkinson's disease. We investigated by PET with [11C]raclopride whether Parkinson's disease progression modifies the striatal changes in synaptic dopamine levels induced by levodopa administration, and whether this modification, if present, could have an impact on the emergence of dyskinesias. We found that, 1 h after oral administration of standard-release 250/25 mg of levodopa/carbidopa, levodopa-induced increases in synaptic dopamine levels (as estimated by striatal changes in [11C]raclopride binding potential) correlated positively with duration of Parkinson's disease symptoms (for the caudate nucleus, r = 0.79, P < 0.001; for the putamen, r = 0.88, P < 0.0001). Patients with peak-dose dyskinesias had larger 1-h increases in synaptic dopamine levels than stable responders, but there were no between-group differences in [11C]raclopride binding 4 h post-levodopa. The corresponding (time × group) interaction term in the repeated measures analysis of covariance was significant, even after adjusting for between-group differences in duration of Parkinson's disease symptoms (for the caudate nucleus, P = 0.030; for the putamen, P = 0.021). Our results indicate that, at the synaptic level, an identical dose of levodopa induces increasingly larger 1-h changes in dopamine levels as Parkinson's disease progresses. Large levodopa-induced increases in synaptic dopamine concentration can lead to dramatic changes in receptor occupancy, which may be responsible for the emergence of peak-dose dyskinesias in Parkinson's disease.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="De La Fuente Ferna Ndez, Rau L" sort="De La Fuente Ferna Ndez, Rau L" uniqKey="De La Fuente Ferna Ndez R" first="Rau L" last="De La Fuente-Ferna Ndez">Rau L De La Fuente-Ferna Ndez</name></noRegion><name sortKey="Calne, Donald B" sort="Calne, Donald B" uniqKey="Calne D" first="Donald B." last="Calne">Donald B. Calne</name><name sortKey="Furtado, Sarah" sort="Furtado, Sarah" uniqKey="Furtado S" first="Sarah" last="Furtado">Sarah Furtado</name><name sortKey="Huang, Zhigao" sort="Huang, Zhigao" uniqKey="Huang Z" first="Zhigao" last="Huang">Zhigao Huang</name><name sortKey="Lu, Jian Qiang" sort="Lu, Jian Qiang" uniqKey="Lu J" first="Jian-Qiang" last="Lu">Jian-Qiang Lu</name><name sortKey="Ruth, Thomas J" sort="Ruth, Thomas J" uniqKey="Ruth T" first="Thomas J." last="Ruth">Thomas J. Ruth</name><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name><name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A. Jon" last="Stoessl">A. Jon Stoessl</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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