Characterisation of striatal NMDA receptors involved in the generation of parkinsonian symptoms: Intrastriatal microinjection studies in the 6‐OHDA‐lesioned rat
Identifieur interne : 000006 ( Istex/Corpus ); précédent : 000005; suivant : 000007Characterisation of striatal NMDA receptors involved in the generation of parkinsonian symptoms: Intrastriatal microinjection studies in the 6‐OHDA‐lesioned rat
Auteurs : Joanne E. Nash ; Jonathan M. BrotchieSource :
- Movement Disorders [ 0885-3185 ] ; 2002-05.
English descriptors
- KwdEn :
Abstract
Treatments for Parkinson's disease based on replacement of lost dopamine have several problems. Following loss of dopamine, enhanced N‐methyl‐D‐aspartate (NMDA) receptor‐mediated transmission in the striatum is thought to be part of the cascade of events leading to the generation of parkinsonian symptoms. We determined the localisation and pharmacological characteristics of NMDA receptors that play a role in generating parkinsonian symptoms within the striatum. Rats were lesioned unilaterally with 6‐hydroxydopamine (6‐OHDA), and cannulae implanted bilaterally to allow injection of a range of NMDA receptor antagonists at different striatal sites. When injected rostrally into the dopamine‐depleted striatum, the glycine site partial agonist, (+)‐HA‐966 (44–400 nmol) caused a dose‐dependent contraversive rotational response consistent with an antiparkinsonian action. (+)‐HA‐966 (400 nmol) had no effect when infused into more caudal regions of the dopamine‐depleted striatum, or following injection into any striatal region on the dopamine‐intact side. To determine the pharmacological profile of NMDA receptors involved in inducing parkinsonism in 6‐OHDA‐lesioned rats, a range of NMDA receptor antagonists was infused directly into the rostral striatum. Ifenprodil (100 nmol) and 7‐chlorokynurenate (37 nmol), but not MK‐801 (15 nmol) or D‐APV (25 nmol) elicited a dramatic rotational response when injected into the dopamine‐depleted striatum. This pharmacological profile is not consistent with an effect mediated via blocking NR2B‐containing NMDA receptors. The effect of intrastriatal injection of ifenprodil was increased in animals previously treated with levodopa (L‐dopa) methyl ester. This was seen as an increase in on‐time and in peak rotational response. We propose that stimulation of NR2B‐containing NMDA receptors in the rostral striatum underlies the generation of parkinsonian symptoms. These studies are in line with previous findings suggesting that administration of NR2B‐selective NMDA receptor antagonists may be therapeutically beneficial for parkinsonian patients, when given de novo and following L‐dopa treatment. © 2002 Movement Disorder Society.
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DOI: 10.1002/mds.10107
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Following loss of dopamine, enhanced N‐methyl‐D‐aspartate (NMDA) receptor‐mediated transmission in the striatum is thought to be part of the cascade of events leading to the generation of parkinsonian symptoms. We determined the localisation and pharmacological characteristics of NMDA receptors that play a role in generating parkinsonian symptoms within the striatum. Rats were lesioned unilaterally with 6‐hydroxydopamine (6‐OHDA), and cannulae implanted bilaterally to allow injection of a range of NMDA receptor antagonists at different striatal sites. When injected rostrally into the dopamine‐depleted striatum, the glycine site partial agonist, (+)‐HA‐966 (44–400 nmol) caused a dose‐dependent contraversive rotational response consistent with an antiparkinsonian action. (+)‐HA‐966 (400 nmol) had no effect when infused into more caudal regions of the dopamine‐depleted striatum, or following injection into any striatal region on the dopamine‐intact side. To determine the pharmacological profile of NMDA receptors involved in inducing parkinsonism in 6‐OHDA‐lesioned rats, a range of NMDA receptor antagonists was infused directly into the rostral striatum. Ifenprodil (100 nmol) and 7‐chlorokynurenate (37 nmol), but not MK‐801 (15 nmol) or D‐APV (25 nmol) elicited a dramatic rotational response when injected into the dopamine‐depleted striatum. This pharmacological profile is not consistent with an effect mediated via blocking NR2B‐containing NMDA receptors. The effect of intrastriatal injection of ifenprodil was increased in animals previously treated with levodopa (L‐dopa) methyl ester. This was seen as an increase in on‐time and in peak rotational response. We propose that stimulation of NR2B‐containing NMDA receptors in the rostral striatum underlies the generation of parkinsonian symptoms. These studies are in line with previous findings suggesting that administration of NR2B‐selective NMDA receptor antagonists may be therapeutically beneficial for parkinsonian patients, when given de novo and following L‐dopa treatment. © 2002 Movement Disorder Society.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Joanne E. Nash PhD</name><affiliations><json:string>Manchester Movement Disorder Laboratory, Division of Neuroscience, School of Biological Sciences, University of Manchester, Manchester, United Kingdom</json:string></affiliations></json:item><json:item><name>Jonathan M. 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Following loss of dopamine, enhanced N‐methyl‐D‐aspartate (NMDA) receptor‐mediated transmission in the striatum is thought to be part of the cascade of events leading to the generation of parkinsonian symptoms. We determined the localisation and pharmacological characteristics of NMDA receptors that play a role in generating parkinsonian symptoms within the striatum. Rats were lesioned unilaterally with 6‐hydroxydopamine (6‐OHDA), and cannulae implanted bilaterally to allow injection of a range of NMDA receptor antagonists at different striatal sites. When injected rostrally into the dopamine‐depleted striatum, the glycine site partial agonist, (+)‐HA‐966 (44–400 nmol) caused a dose‐dependent contraversive rotational response consistent with an antiparkinsonian action. (+)‐HA‐966 (400 nmol) had no effect when infused into more caudal regions of the dopamine‐depleted striatum, or following injection into any striatal region on the dopamine‐intact side. To determine the pharmacological profile of NMDA receptors involved in inducing parkinsonism in 6‐OHDA‐lesioned rats, a range of NMDA receptor antagonists was infused directly into the rostral striatum. Ifenprodil (100 nmol) and 7‐chlorokynurenate (37 nmol), but not MK‐801 (15 nmol) or D‐APV (25 nmol) elicited a dramatic rotational response when injected into the dopamine‐depleted striatum. This pharmacological profile is not consistent with an effect mediated via blocking NR2B‐containing NMDA receptors. The effect of intrastriatal injection of ifenprodil was increased in animals previously treated with levodopa (L‐dopa) methyl ester. This was seen as an increase in on‐time and in peak rotational response. We propose that stimulation of NR2B‐containing NMDA receptors in the rostral striatum underlies the generation of parkinsonian symptoms. 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To determine the pharmacological profile of NMDA receptors involved in inducing parkinsonism in 6‐OHDA‐lesioned rats, a range of NMDA receptor antagonists was infused directly into the rostral striatum. Ifenprodil (100 nmol) and 7‐chlorokynurenate (37 nmol), but not MK‐801 (15 nmol) or D‐APV (25 nmol) elicited a dramatic rotational response when injected into the dopamine‐depleted striatum. This pharmacological profile is not consistent with an effect mediated via blocking NR2B‐containing NMDA receptors. The effect of intrastriatal injection of ifenprodil was increased in animals previously treated with levodopa (L‐dopa) methyl ester. This was seen as an increase in on‐time and in peak rotational response. We propose that stimulation of NR2B‐containing NMDA receptors in the rostral striatum underlies the generation of parkinsonian symptoms. 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Following loss of dopamine, enhanced N‐methyl‐D‐aspartate (NMDA) receptor‐mediated transmission in the striatum is thought to be part of the cascade of events leading to the generation of parkinsonian symptoms. We determined the localisation and pharmacological characteristics of NMDA receptors that play a role in generating parkinsonian symptoms within the striatum. Rats were lesioned unilaterally with 6‐hydroxydopamine (6‐OHDA), and cannulae implanted bilaterally to allow injection of a range of NMDA receptor antagonists at different striatal sites. When injected rostrally into the dopamine‐depleted striatum, the glycine site partial agonist, (+)‐HA‐966 (44–400 nmol) caused a dose‐dependent contraversive rotational response consistent with an antiparkinsonian action. (+)‐HA‐966 (400 nmol) had no effect when infused into more caudal regions of the dopamine‐depleted striatum, or following injection into any striatal region on the dopamine‐intact side. To determine the pharmacological profile of NMDA receptors involved in inducing parkinsonism in 6‐OHDA‐lesioned rats, a range of NMDA receptor antagonists was infused directly into the rostral striatum. Ifenprodil (100 nmol) and 7‐chlorokynurenate (37 nmol), but not MK‐801 (15 nmol) or D‐APV (25 nmol) elicited a dramatic rotational response when injected into the dopamine‐depleted striatum. This pharmacological profile is not consistent with an effect mediated via blocking NR2B‐containing NMDA receptors. The effect of intrastriatal injection of ifenprodil was increased in animals previously treated with levodopa (<sc>L</sc>‐dopa) methyl ester. This was seen as an increase in on‐time and in peak rotational response. We propose that stimulation of NR2B‐containing NMDA receptors in the rostral striatum underlies the generation of parkinsonian symptoms. These studies are in line with previous findings suggesting that administration of NR2B‐selective NMDA receptor antagonists may be therapeutically beneficial for parkinsonian patients, when given de novo and following <sc>L</sc>‐dopa treatment. © 2002 Movement Disorder Society.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><!--Version 0.6 générée le 4-12-2015--><mods version="3.6"><titleInfo lang="en"><title>Characterisation of striatal NMDA receptors involved in the generation of parkinsonian symptoms: Intrastriatal microinjection studies in the 6‐OHDA‐lesioned rat</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>NMDA Receptors and the 6‐OHDA RA</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Characterisation of striatal NMDA receptors involved in the generation of parkinsonian symptoms: Intrastriatal microinjection studies in the 6‐OHDA‐lesioned rat</title></titleInfo><name type="personal"><namePart type="given">Joanne E.</namePart><namePart type="family">Nash</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Manchester Movement Disorder Laboratory, Division of Neuroscience, School of Biological Sciences, University of Manchester, Manchester, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jonathan M.</namePart><namePart type="family">Brotchie</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Manchester Movement Disorder Laboratory, Division of Neuroscience, School of Biological Sciences, University of Manchester, Manchester, United Kingdom</affiliation><description>Correspondence: Manchester Movement Disorder Laboratory, Room 1.124, Division of Neuroscience, School of Biological Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, United Kingdom, and Motac Neuroscience Ltd, The Incubator Building, Grafton St., Manchester M13 9XX, United Kingdom</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre authority="originalCategForm">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">New York</placeTerm></place><dateIssued encoding="w3cdtf">2002-05</dateIssued><dateCaptured encoding="w3cdtf">2000-12-13</dateCaptured><dateValid encoding="w3cdtf">2001-05-23</dateValid><copyrightDate encoding="w3cdtf">2002</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">6</extent><extent unit="references">109</extent><extent unit="words">7517</extent></physicalDescription><abstract lang="en">Treatments for Parkinson's disease based on replacement of lost dopamine have several problems. Following loss of dopamine, enhanced N‐methyl‐D‐aspartate (NMDA) receptor‐mediated transmission in the striatum is thought to be part of the cascade of events leading to the generation of parkinsonian symptoms. We determined the localisation and pharmacological characteristics of NMDA receptors that play a role in generating parkinsonian symptoms within the striatum. Rats were lesioned unilaterally with 6‐hydroxydopamine (6‐OHDA), and cannulae implanted bilaterally to allow injection of a range of NMDA receptor antagonists at different striatal sites. When injected rostrally into the dopamine‐depleted striatum, the glycine site partial agonist, (+)‐HA‐966 (44–400 nmol) caused a dose‐dependent contraversive rotational response consistent with an antiparkinsonian action. (+)‐HA‐966 (400 nmol) had no effect when infused into more caudal regions of the dopamine‐depleted striatum, or following injection into any striatal region on the dopamine‐intact side. To determine the pharmacological profile of NMDA receptors involved in inducing parkinsonism in 6‐OHDA‐lesioned rats, a range of NMDA receptor antagonists was infused directly into the rostral striatum. Ifenprodil (100 nmol) and 7‐chlorokynurenate (37 nmol), but not MK‐801 (15 nmol) or D‐APV (25 nmol) elicited a dramatic rotational response when injected into the dopamine‐depleted striatum. This pharmacological profile is not consistent with an effect mediated via blocking NR2B‐containing NMDA receptors. The effect of intrastriatal injection of ifenprodil was increased in animals previously treated with levodopa (L‐dopa) methyl ester. This was seen as an increase in on‐time and in peak rotational response. We propose that stimulation of NR2B‐containing NMDA receptors in the rostral striatum underlies the generation of parkinsonian symptoms. These studies are in line with previous findings suggesting that administration of NR2B‐selective NMDA receptor antagonists may be therapeutically beneficial for parkinsonian patients, when given de novo and following L‐dopa treatment. © 2002 Movement Disorder Society.</abstract><subject lang="en"><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>NMDA receptor antagonists</topic><topic>striatum</topic><topic>6‐OHDA‐lesioned rat</topic><topic>globus pallidus</topic><topic>basal ganglia</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title><subTitle>Official Journal of the Movement Disorder Society</subTitle></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><subject><genre>article category</genre><topic>Research Articles</topic></subject><identifier type="ISSN">0885-3185</identifier><identifier type="eISSN">1531-8257</identifier><identifier type="DOI">10.1002/(ISSN)1531-8257</identifier><identifier type="PublisherID">MDS</identifier><part><date>2002</date><detail type="volume"><caption>vol.</caption><number>17</number></detail><detail type="issue"><caption>no.</caption><number>3</number></detail><extent unit="pages"><start>455</start><end>466</end><total>12</total></extent></part></relatedItem><identifier type="istex">62361BA501CDDD7FA8BF244FFD50A0509E7D82B2</identifier><identifier type="DOI">10.1002/mds.10107</identifier><identifier type="ArticleID">MDS10107</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2002 Movement Disorders Society</accessCondition><recordInfo><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin><recordContentSource>WILEY</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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