Metabotropic glutamate 7 receptor subtype modulates motor symptoms in rodent models of Parkinson's disease.
Identifieur interne : 000A99 ( PubMed/Corpus ); précédent : 000A98; suivant : 000B00Metabotropic glutamate 7 receptor subtype modulates motor symptoms in rodent models of Parkinson's disease.
Auteurs : B. Greco ; S. Lopez ; H. Van Der Putten ; P J Flor ; M. AmalricSource :
- The Journal of pharmacology and experimental therapeutics [ 1521-0103 ] ; 2010.
English descriptors
- KwdEn :
- Allosteric Regulation, Animals, Apomorphine (pharmacology), Benzhydryl Compounds (pharmacology), Catalepsy (chemically induced), Catalepsy (physiopathology), Disease Models, Animal, Haloperidol, Male, Mice, Mice, Knockout, Oxidopamine, Parkinson Disease, Secondary (chemically induced), Parkinson Disease, Secondary (physiopathology), Rats, Rats, Wistar, Reaction Time (drug effects), Receptors, Metabotropic Glutamate (agonists), Receptors, Metabotropic Glutamate (genetics), Receptors, Metabotropic Glutamate (physiology), Stereotyped Behavior (drug effects).
- MESH :
- chemical , agonists : Receptors, Metabotropic Glutamate.
- chemical , genetics : Receptors, Metabotropic Glutamate.
- chemical , pharmacology : Apomorphine, Benzhydryl Compounds.
- chemically induced : Catalepsy, Parkinson Disease, Secondary.
- drug effects : Reaction Time, Stereotyped Behavior.
- chemical , physiology : Receptors, Metabotropic Glutamate.
- physiopathology : Catalepsy, Parkinson Disease, Secondary.
- Allosteric Regulation, Animals, Disease Models, Animal, Haloperidol, Male, Mice, Mice, Knockout, Oxidopamine, Rats, Rats, Wistar.
Abstract
Metabotropic glutamate (mGlu) receptors modulate synaptic transmission in the central nervous system and represent promising therapeutic targets for symptomatic treatment of Parkinson's disease (PD). Among the eight mGlu receptor subtypes, mGlu7 receptor is prominently expressed in the basal ganglia, but its role in restoring motor function in animal models of PD is not known. The effects of N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082), the first selective allosteric activator of mGlu7 receptors, were thus tested in different rodent models of PD. Here, we show that oral (5 mg/kg) or intrastriatal administration (0.1 and 0.5 nmol) of AMN082 reverses haloperidol-induced catalepsy in rats. AMN082 (2.5 and 5 mg/kg) reduces apomorphine-induced rotations in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. In a more complex task commonly used to evaluate major akinetic symptoms of PD patients, 5 mg/kg AMN082 reverses the increased reaction time to respond to a cue of bilateral 6-OHDA-lesioned rats. In addition, AMN082 reduces the duration of haloperidol-induced catalepsy in a mGlu7 receptor-dependent manner in wild-type but not mGlu7 receptor knockout mice. Higher doses of AMN082 (10 and 20 mg/kg p.o.) have no effect on the same models of PD. Overall these findings suggest that mGlu7 receptor activation can reverse motor dysfunction associated with reduced dopamine activity. Selective ligands of mGlu7 receptor subtypes may thus be considered as promising compounds for the development of antiparkinsonian therapeutic strategies.
DOI: 10.1124/jpet.109.162115
PubMed: 19940105
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Van Der Putten</name></author><author><name sortKey="Flor, P J" sort="Flor, P J" uniqKey="Flor P" first="P J" last="Flor">P J Flor</name></author><author><name sortKey="Amalric, M" sort="Amalric, M" uniqKey="Amalric M" first="M" last="Amalric">M. Amalric</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2010">2010</date><idno type="RBID">pubmed:19940105</idno><idno type="pmid">19940105</idno><idno type="doi">10.1124/jpet.109.162115</idno><idno type="wicri:Area/PubMed/Corpus">000A99</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000A99</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Metabotropic glutamate 7 receptor subtype modulates motor symptoms in rodent models of Parkinson's disease.</title><author><name sortKey="Greco, B" sort="Greco, B" uniqKey="Greco B" first="B" last="Greco">B. Greco</name><affiliation><nlm:affiliation>Laboratoire de Neurobiologie de la Cognition, Unité Mixte de Recherche 6155 Centre National de la Recherche Scientifique, Université Aix-Marseille, Case C, 3 Place Victor Hugo, 13331 Marseille cedex 3, France.</nlm:affiliation></affiliation></author><author><name sortKey="Lopez, S" sort="Lopez, S" uniqKey="Lopez S" first="S" last="Lopez">S. Lopez</name></author><author><name sortKey="Van Der Putten, H" sort="Van Der Putten, H" uniqKey="Van Der Putten H" first="H" last="Van Der Putten">H. Van Der Putten</name></author><author><name sortKey="Flor, P J" sort="Flor, P J" uniqKey="Flor P" first="P J" last="Flor">P J Flor</name></author><author><name sortKey="Amalric, M" sort="Amalric, M" uniqKey="Amalric M" first="M" last="Amalric">M. Amalric</name></author></analytic><series><title level="j">The Journal of pharmacology and experimental therapeutics</title><idno type="eISSN">1521-0103</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Allosteric Regulation</term><term>Animals</term><term>Apomorphine (pharmacology)</term><term>Benzhydryl Compounds (pharmacology)</term><term>Catalepsy (chemically induced)</term><term>Catalepsy (physiopathology)</term><term>Disease Models, Animal</term><term>Haloperidol</term><term>Male</term><term>Mice</term><term>Mice, Knockout</term><term>Oxidopamine</term><term>Parkinson Disease, Secondary (chemically induced)</term><term>Parkinson Disease, Secondary (physiopathology)</term><term>Rats</term><term>Rats, Wistar</term><term>Reaction Time (drug effects)</term><term>Receptors, Metabotropic Glutamate (agonists)</term><term>Receptors, Metabotropic Glutamate (genetics)</term><term>Receptors, Metabotropic Glutamate (physiology)</term><term>Stereotyped Behavior (drug effects)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="agonists" xml:lang="en"><term>Receptors, Metabotropic Glutamate</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Receptors, Metabotropic Glutamate</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Apomorphine</term><term>Benzhydryl Compounds</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Catalepsy</term><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Reaction Time</term><term>Stereotyped Behavior</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Receptors, Metabotropic Glutamate</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Catalepsy</term><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Allosteric Regulation</term><term>Animals</term><term>Disease Models, Animal</term><term>Haloperidol</term><term>Male</term><term>Mice</term><term>Mice, Knockout</term><term>Oxidopamine</term><term>Rats</term><term>Rats, Wistar</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Metabotropic glutamate (mGlu) receptors modulate synaptic transmission in the central nervous system and represent promising therapeutic targets for symptomatic treatment of Parkinson's disease (PD). Among the eight mGlu receptor subtypes, mGlu7 receptor is prominently expressed in the basal ganglia, but its role in restoring motor function in animal models of PD is not known. The effects of N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082), the first selective allosteric activator of mGlu7 receptors, were thus tested in different rodent models of PD. Here, we show that oral (5 mg/kg) or intrastriatal administration (0.1 and 0.5 nmol) of AMN082 reverses haloperidol-induced catalepsy in rats. AMN082 (2.5 and 5 mg/kg) reduces apomorphine-induced rotations in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. In a more complex task commonly used to evaluate major akinetic symptoms of PD patients, 5 mg/kg AMN082 reverses the increased reaction time to respond to a cue of bilateral 6-OHDA-lesioned rats. In addition, AMN082 reduces the duration of haloperidol-induced catalepsy in a mGlu7 receptor-dependent manner in wild-type but not mGlu7 receptor knockout mice. Higher doses of AMN082 (10 and 20 mg/kg p.o.) have no effect on the same models of PD. Overall these findings suggest that mGlu7 receptor activation can reverse motor dysfunction associated with reduced dopamine activity. Selective ligands of mGlu7 receptor subtypes may thus be considered as promising compounds for the development of antiparkinsonian therapeutic strategies.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">19940105</PMID><DateCreated><Year>2010</Year><Month>02</Month><Day>23</Day></DateCreated><DateCompleted><Year>2010</Year><Month>04</Month><Day>13</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1521-0103</ISSN><JournalIssue CitedMedium="Internet"><Volume>332</Volume><Issue>3</Issue><PubDate><Year>2010</Year><Month>Mar</Month></PubDate></JournalIssue><Title>The Journal of pharmacology and experimental therapeutics</Title><ISOAbbreviation>J. Pharmacol. Exp. Ther.</ISOAbbreviation></Journal><ArticleTitle>Metabotropic glutamate 7 receptor subtype modulates motor symptoms in rodent models of Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>1064-71</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1124/jpet.109.162115</ELocationID><Abstract><AbstractText>Metabotropic glutamate (mGlu) receptors modulate synaptic transmission in the central nervous system and represent promising therapeutic targets for symptomatic treatment of Parkinson's disease (PD). Among the eight mGlu receptor subtypes, mGlu7 receptor is prominently expressed in the basal ganglia, but its role in restoring motor function in animal models of PD is not known. The effects of N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082), the first selective allosteric activator of mGlu7 receptors, were thus tested in different rodent models of PD. Here, we show that oral (5 mg/kg) or intrastriatal administration (0.1 and 0.5 nmol) of AMN082 reverses haloperidol-induced catalepsy in rats. AMN082 (2.5 and 5 mg/kg) reduces apomorphine-induced rotations in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. In a more complex task commonly used to evaluate major akinetic symptoms of PD patients, 5 mg/kg AMN082 reverses the increased reaction time to respond to a cue of bilateral 6-OHDA-lesioned rats. In addition, AMN082 reduces the duration of haloperidol-induced catalepsy in a mGlu7 receptor-dependent manner in wild-type but not mGlu7 receptor knockout mice. Higher doses of AMN082 (10 and 20 mg/kg p.o.) have no effect on the same models of PD. Overall these findings suggest that mGlu7 receptor activation can reverse motor dysfunction associated with reduced dopamine activity. Selective ligands of mGlu7 receptor subtypes may thus be considered as promising compounds for the development of antiparkinsonian therapeutic strategies.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Greco</LastName><ForeName>B</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Laboratoire de Neurobiologie de la Cognition, Unité Mixte de Recherche 6155 Centre National de la Recherche Scientifique, Université Aix-Marseille, Case C, 3 Place Victor Hugo, 13331 Marseille cedex 3, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lopez</LastName><ForeName>S</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>van der Putten</LastName><ForeName>H</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>Flor</LastName><ForeName>P J</ForeName><Initials>PJ</Initials></Author><Author ValidYN="Y"><LastName>Amalric</LastName><ForeName>M</ForeName><Initials>M</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2009</Year><Month>11</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Pharmacol Exp Ther</MedlineTA><NlmUniqueID>0376362</NlmUniqueID><ISSNLinking>0022-3565</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001559">Benzhydryl Compounds</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C507346">N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018094">Receptors, Metabotropic Glutamate</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C102719">metabotropic glutamate receptor 7</NameOfSubstance></Chemical><Chemical><RegistryNumber>8HW4YBZ748</RegistryNumber><NameOfSubstance UI="D016627">Oxidopamine</NameOfSubstance></Chemical><Chemical><RegistryNumber>J6292F8L3D</RegistryNumber><NameOfSubstance UI="D006220">Haloperidol</NameOfSubstance></Chemical><Chemical><RegistryNumber>N21FAR7B4S</RegistryNumber><NameOfSubstance UI="D001058">Apomorphine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000494" MajorTopicYN="N">Allosteric Regulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001058" MajorTopicYN="N">Apomorphine</DescriptorName><QualifierName UI="Q000494" 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