Subthalamic deep brain stimulation differently alters striatal dopaminergic receptor levels in rats.
Identifieur interne : 000270 ( PubMed/Checkpoint ); précédent : 000269; suivant : 000271Subthalamic deep brain stimulation differently alters striatal dopaminergic receptor levels in rats.
Auteurs : Carole Carcenac [France] ; Mathieu Favier [France] ; Yvan Vachez [France] ; Emilie Lacombe [France] ; Sébastien Carnicella [France] ; Marc Savasta [France] ; Sabrina Boulet [France]Source :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2015.
English descriptors
- KwdEn :
- Adrenergic Agents (pharmacology), Animals, Corpus Striatum (drug effects), Corpus Striatum (metabolism), Deep Brain Stimulation, Dopamine Agents (pharmacology), Dopaminergic Neurons (drug effects), Functional Laterality (drug effects), Gene Expression Regulation (drug effects), Oxidopamine (pharmacology), Protein Binding (drug effects), Radioisotopes (pharmacokinetics), Rats, Receptors, Dopamine (genetics), Receptors, Dopamine (metabolism), Subthalamic Nucleus (physiology), Tyrosine 3-Monooxygenase (metabolism).
- MESH :
- chemical , genetics : Receptors, Dopamine.
- chemical , metabolism : Receptors, Dopamine, Tyrosine 3-Monooxygenase.
- chemical , pharmacokinetics : Radioisotopes.
- chemical , pharmacology : Adrenergic Agents, Dopamine Agents, Oxidopamine.
- drug effects : Corpus Striatum, Dopaminergic Neurons, Functional Laterality, Gene Expression Regulation, Protein Binding.
- metabolism : Corpus Striatum.
- physiology : Subthalamic Nucleus.
- Animals, Deep Brain Stimulation, Rats.
Abstract
High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is recognized as an effective treatment for the motor symptoms of Parkinson's disease (PD), but its mechanisms, particularly as concern dopaminergic transmission, remain unclear. The aim of this study was to evaluate changes in the expression of dopaminergic receptors (D1, D2, and D3 receptors) after prolonged (4 h) unilateral STN-HFS in anesthetized intact rats and rats with total dopaminergic denervation. We used [(3)H]SCH 23390, [(125)I]iodosulpride, and [(125)I]OH-PIPAT to assess the densities of D1R, D2R, and D3R, respectively, within different areas of the striatum-a major input structure of the basal ganglia-including the nucleus accumbens. We found that STN-HFS increased D1 R levels in almost all of the striatal areas examined, in both intact and denervated rats. By contrast, STN-HFS led to a large decrease in D2 R and D3R levels, limited to the nucleus accumbens and independent of the dopaminergic state of the animals. These data suggest that the influence of STN-HFS on striatal D1 R expression may contribute to its therapeutic effects on motor symptoms, whereas its impact on D2R/D3 R levels in the nucleus accumbens may account for the neuropsychiatric side effects often observed in stimulated PD patients, such as postoperative apathy.
DOI: 10.1002/mds.26146
PubMed: 25588931
Affiliations:
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pubmed:25588931Le document en format XML
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<front><div type="abstract" xml:lang="en">High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is recognized as an effective treatment for the motor symptoms of Parkinson's disease (PD), but its mechanisms, particularly as concern dopaminergic transmission, remain unclear. The aim of this study was to evaluate changes in the expression of dopaminergic receptors (D1, D2, and D3 receptors) after prolonged (4 h) unilateral STN-HFS in anesthetized intact rats and rats with total dopaminergic denervation. We used [(3)H]SCH 23390, [(125)I]iodosulpride, and [(125)I]OH-PIPAT to assess the densities of D1R, D2R, and D3R, respectively, within different areas of the striatum-a major input structure of the basal ganglia-including the nucleus accumbens. We found that STN-HFS increased D1 R levels in almost all of the striatal areas examined, in both intact and denervated rats. By contrast, STN-HFS led to a large decrease in D2 R and D3R levels, limited to the nucleus accumbens and independent of the dopaminergic state of the animals. These data suggest that the influence of STN-HFS on striatal D1 R expression may contribute to its therapeutic effects on motor symptoms, whereas its impact on D2R/D3 R levels in the nucleus accumbens may account for the neuropsychiatric side effects often observed in stimulated PD patients, such as postoperative apathy.</div>
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<Abstract><AbstractText>High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is recognized as an effective treatment for the motor symptoms of Parkinson's disease (PD), but its mechanisms, particularly as concern dopaminergic transmission, remain unclear. The aim of this study was to evaluate changes in the expression of dopaminergic receptors (D1, D2, and D3 receptors) after prolonged (4 h) unilateral STN-HFS in anesthetized intact rats and rats with total dopaminergic denervation. We used [(3)H]SCH 23390, [(125)I]iodosulpride, and [(125)I]OH-PIPAT to assess the densities of D1R, D2R, and D3R, respectively, within different areas of the striatum-a major input structure of the basal ganglia-including the nucleus accumbens. We found that STN-HFS increased D1 R levels in almost all of the striatal areas examined, in both intact and denervated rats. By contrast, STN-HFS led to a large decrease in D2 R and D3R levels, limited to the nucleus accumbens and independent of the dopaminergic state of the animals. These data suggest that the influence of STN-HFS on striatal D1 R expression may contribute to its therapeutic effects on motor symptoms, whereas its impact on D2R/D3 R levels in the nucleus accumbens may account for the neuropsychiatric side effects often observed in stimulated PD patients, such as postoperative apathy.</AbstractText>
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<AffiliationInfo><Affiliation>Centre Hospitalier Universitaire de Grenoble, Grenoble, France.</Affiliation>
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<MedlineTA>Mov Disord</MedlineTA>
<NlmUniqueID>8610688</NlmUniqueID>
<ISSNLinking>0885-3185</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D018663">Adrenergic Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D015259">Dopamine Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
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<Chemical><RegistryNumber>0</RegistryNumber>
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<Chemical><RegistryNumber>8HW4YBZ748</RegistryNumber>
<NameOfSubstance UI="D016627">Oxidopamine</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 1.14.16.2</RegistryNumber>
<NameOfSubstance UI="D014446">Tyrosine 3-Monooxygenase</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D018663" MajorTopicYN="N">Adrenergic Agents</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003342" MajorTopicYN="N">Corpus Striatum</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D046690" MajorTopicYN="Y">Deep Brain Stimulation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015259" MajorTopicYN="N">Dopamine Agents</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D059290" MajorTopicYN="N">Dopaminergic Neurons</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007839" MajorTopicYN="N">Functional Laterality</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005786" MajorTopicYN="N">Gene Expression Regulation</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016627" MajorTopicYN="N">Oxidopamine</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011485" MajorTopicYN="N">Protein Binding</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011868" MajorTopicYN="N">Radioisotopes</DescriptorName>
<QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011954" MajorTopicYN="N">Receptors, Dopamine</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D020531" MajorTopicYN="N">Subthalamic Nucleus</DescriptorName>
<QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014446" MajorTopicYN="N">Tyrosine 3-Monooxygenase</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Parkinson's disease</Keyword>
<Keyword MajorTopicYN="N">dopamine receptors</Keyword>
<Keyword MajorTopicYN="N">nucleus accumbens</Keyword>
<Keyword MajorTopicYN="N">striatum</Keyword>
<Keyword MajorTopicYN="N">subthalamic nucleus high-frequency stimulation</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year>
<Month>05</Month>
<Day>29</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2014</Year>
<Month>12</Month>
<Day>02</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2014</Year>
<Month>12</Month>
<Day>05</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2015</Year>
<Month>1</Month>
<Day>16</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2015</Year>
<Month>1</Month>
<Day>16</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2016</Year>
<Month>10</Month>
<Day>13</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">25588931</ArticleId>
<ArticleId IdType="doi">10.1002/mds.26146</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>France</li>
</country>
<region><li>Auvergne-Rhône-Alpes</li>
<li>Rhône-Alpes</li>
</region>
<settlement><li>Grenoble</li>
</settlement>
</list>
<tree><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Carcenac, Carole" sort="Carcenac, Carole" uniqKey="Carcenac C" first="Carole" last="Carcenac">Carole Carcenac</name>
</region>
<name sortKey="Boulet, Sabrina" sort="Boulet, Sabrina" uniqKey="Boulet S" first="Sabrina" last="Boulet">Sabrina Boulet</name>
<name sortKey="Carnicella, Sebastien" sort="Carnicella, Sebastien" uniqKey="Carnicella S" first="Sébastien" last="Carnicella">Sébastien Carnicella</name>
<name sortKey="Favier, Mathieu" sort="Favier, Mathieu" uniqKey="Favier M" first="Mathieu" last="Favier">Mathieu Favier</name>
<name sortKey="Lacombe, Emilie" sort="Lacombe, Emilie" uniqKey="Lacombe E" first="Emilie" last="Lacombe">Emilie Lacombe</name>
<name sortKey="Savasta, Marc" sort="Savasta, Marc" uniqKey="Savasta M" first="Marc" last="Savasta">Marc Savasta</name>
<name sortKey="Vachez, Yvan" sort="Vachez, Yvan" uniqKey="Vachez Y" first="Yvan" last="Vachez">Yvan Vachez</name>
</country>
</tree>
</affiliations>
</record>
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