Subthalamic deep brain stimulation differently alters striatal dopaminergic receptor levels in rats.
Identifieur interne : 000500 ( Main/Exploration ); précédent : 000499; suivant : 000501Subthalamic 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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uniqKey="Carcenac C" first="Carole" last="Carcenac">Carole Carcenac</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation></author><author><name sortKey="Favier, Mathieu" sort="Favier, Mathieu" uniqKey="Favier M" first="Mathieu" last="Favier">Mathieu Favier</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation></author><author><name sortKey="Vachez, Yvan" sort="Vachez, Yvan" uniqKey="Vachez Y" first="Yvan" last="Vachez">Yvan Vachez</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation></author><author><name sortKey="Lacombe, Emilie" sort="Lacombe, Emilie" uniqKey="Lacombe E" first="Emilie" last="Lacombe">Emilie Lacombe</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation></author><author><name sortKey="Carnicella, Sebastien" sort="Carnicella, Sebastien" uniqKey="Carnicella S" first="Sébastien" last="Carnicella">Sébastien Carnicella</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation></author><author><name sortKey="Savasta, Marc" sort="Savasta, Marc" uniqKey="Savasta M" first="Marc" last="Savasta">Marc Savasta</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation></author><author><name sortKey="Boulet, Sabrina" sort="Boulet, Sabrina" uniqKey="Boulet S" first="Sabrina" last="Boulet">Sabrina Boulet</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adrenergic Agents (pharmacology)</term><term>Animals</term><term>Corpus Striatum (drug effects)</term><term>Corpus Striatum (metabolism)</term><term>Deep Brain Stimulation</term><term>Dopamine Agents (pharmacology)</term><term>Dopaminergic Neurons (drug effects)</term><term>Functional Laterality (drug effects)</term><term>Gene Expression Regulation (drug effects)</term><term>Oxidopamine (pharmacology)</term><term>Protein Binding (drug effects)</term><term>Radioisotopes (pharmacokinetics)</term><term>Rats</term><term>Receptors, Dopamine (genetics)</term><term>Receptors, Dopamine (metabolism)</term><term>Subthalamic Nucleus (physiology)</term><term>Tyrosine 3-Monooxygenase (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Receptors, Dopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Receptors, Dopamine</term><term>Tyrosine 3-Monooxygenase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Radioisotopes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Adrenergic Agents</term><term>Dopamine Agents</term><term>Oxidopamine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Corpus Striatum</term><term>Dopaminergic Neurons</term><term>Functional Laterality</term><term>Gene Expression Regulation</term><term>Protein Binding</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Corpus Striatum</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Subthalamic Nucleus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Deep Brain Stimulation</term><term>Rats</term></keywords></textClass></profileDesc></teiHeader><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></front></TEI><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>Pour manipuler ce document sous Unix (Dilib)
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