ParkinsonFranceV1, PascalFrancis, Corpus, bibRecord, 000366

An improved model to investigate the efficacy of antidyskinetic agents in hemiparkinsonian rats

Identifieur interne : 000366 ( PascalFrancis/Corpus ); précédent : 000365; suivant : 000367

An improved model to investigate the efficacy of antidyskinetic agents in hemiparkinsonian rats

Auteurs : Brigitte Spinnewyn ; Christelle Charnet ; Sylvie Cornet ; Veronique Roubert ; Pierre-Etienne Chabrier ; Michel Auguet

Source :

Fundamental & clinical pharmacology [ 0767-3981 ] ; 2011.

RBID : Pascal:11-0418967

Descripteurs français

Pascal (Inist)
- Modèle, Efficacité traitement, Animal, Rat, Oxidopamine, Dyskinésie, Lévodopa, Maladie de Parkinson, Contrôle moteur.

English descriptors

KwdEn :
- Animal, Dyskinesia, Levodopa, Models, Motor control, Oxidopamine, Parkinson disease, Rat, Treatment efficiency.

Abstract

A number of experimental models of _L-DOPA-induced dyskinesia have been proposed, but these models result in a low to medium rate of dyskinetic animals with mild to severe symptoms. The objective of this study was to combine a model of 6-OHDA-induced parkinsonism and of _L-DOPA-induced dyskinesia in rats to establish a reliable preclinical model. Two stereotaxic injections of 6-OHDA were administered in the left striatum. This model led to 90-100% of rats with a marked contralateral circling behaviour, significant limb use asymmetry (20%), a decrease in ipsilateral striatal dopamine content (70%) and degeneration of dopamine neurons in the substantia nigra (70%). Chronic treatment with L-DOPA was administered for 35 days and consisted of three phases with incremental daily doses. The third phase resulted in 83-90% of rats developing severe abnormal involuntary movements (AIMs) which included limb and locomotive dyskinesia, axial dystonia and orolingual dyskinesia. Reproducibility of the model, criteria of strict blinding, placebo-controlled design, randomization of study subjects and pretrial determination of sample size were used to measure efficacy of amantadine and istradefylline and to validate the protocol design. Acute or subchronic post-treatment with amantadine reduced the severity of dyskinesia while istradefylline punctually attenuated AIMs. Our experimental conditions using gradual development of dyskinesia induced by increasing doses of _L-DOPA resulted in a reliable model of _L-DOPA-induced dyskinesia with a high rate of dyskinetic rats.

Notice en format standard (ISO 2709)

Pour connaître la documentation sur le format Inist Standard.

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Format Inist (serveur)

NO :	PASCAL 11-0418967 INIST
ET :	An improved model to investigate the efficacy of antidyskinetic agents in hemiparkinsonian rats
AU :	SPINNEWYN (Brigitte); CHARNET (Christelle); CORNET (Sylvie); ROUBERT (Veronique); CHABRIER (Pierre-Etienne); AUGUET (Michel)
AF :	Ipsen Innovation, 5 avenue du Canada/91940 Les Ulis/France (1 aut., 2 aut., 3 aut., 4 aut., 5 aut., 6 aut.)
DT :	Publication en série; Niveau analytique
SO :	Fundamental & clinical pharmacology; ISSN 0767-3981; Coden FCPHEZ; Royaume-Uni; Da. 2011; Vol. 25; No. 5; Pp. 608-618; Bibl. 43 ref.
LA :	Anglais
EA :	A number of experimental models of _L-DOPA-induced dyskinesia have been proposed, but these models result in a low to medium rate of dyskinetic animals with mild to severe symptoms. The objective of this study was to combine a model of 6-OHDA-induced parkinsonism and of _L-DOPA-induced dyskinesia in rats to establish a reliable preclinical model. Two stereotaxic injections of 6-OHDA were administered in the left striatum. This model led to 90-100% of rats with a marked contralateral circling behaviour, significant limb use asymmetry (20%), a decrease in ipsilateral striatal dopamine content (70%) and degeneration of dopamine neurons in the substantia nigra (70%). Chronic treatment with L-DOPA was administered for 35 days and consisted of three phases with incremental daily doses. The third phase resulted in 83-90% of rats developing severe abnormal involuntary movements (AIMs) which included limb and locomotive dyskinesia, axial dystonia and orolingual dyskinesia. Reproducibility of the model, criteria of strict blinding, placebo-controlled design, randomization of study subjects and pretrial determination of sample size were used to measure efficacy of amantadine and istradefylline and to validate the protocol design. Acute or subchronic post-treatment with amantadine reduced the severity of dyskinesia while istradefylline punctually attenuated AIMs. Our experimental conditions using gradual development of dyskinesia induced by increasing doses of _L-DOPA resulted in a reliable model of _L-DOPA-induced dyskinesia with a high rate of dyskinetic rats.
CC :	002B02; 002B17A01; 002B17G
FD :	Modèle; Efficacité traitement; Animal; Rat; Oxidopamine; Dyskinésie; Lévodopa; Maladie de Parkinson; Contrôle moteur
FG :	Rodentia; Mammalia; Vertebrata; Agoniste; Récepteur adrénergique; Sympathomimétique; Syndrome extrapyramidal; Mouvement involontaire; Pathologie du système nerveux; Trouble neurologique; Récepteur dopaminergique D2; Antiparkinsonien; Maladie dégénérative; Pathologie de l'encéphale; Pathologie du système nerveux central
ED :	Models; Treatment efficiency; Animal; Rat; Oxidopamine; Dyskinesia; Levodopa; Parkinson disease; Motor control
EG :	Rodentia; Mammalia; Vertebrata; Agonist; Adrenergic receptor; Sympathomimetic; Extrapyramidal syndrome; Involuntary movement; Nervous system diseases; Neurological disorder; D2 Dopamine receptor; Antiparkinson agent; Degenerative disease; Cerebral disorder; Central nervous system disease
SD :	Modelo; Eficacia tratamiento; Animal; Rata; Oxidopamina; Disquinesia; Levodopa; Parkinson enfermedad; Control motor
LO :	INIST-14711.354000191207660070
ID :	11-0418967

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Pascal:11-0418967

Le document en format XML

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<front><div type="abstract" xml:lang="en">A number of experimental models of <sub>L</sub>
-DOPA-induced dyskinesia have been proposed, but these models result in a low to medium rate of dyskinetic animals with mild to severe symptoms. The objective of this study was to combine a model of 6-OHDA-induced parkinsonism and of <sub>L</sub>
-DOPA-induced dyskinesia in rats to establish a reliable preclinical model. Two stereotaxic injections of 6-OHDA were administered in the left striatum. This model led to 90-100% of rats with a marked contralateral circling behaviour, significant limb use asymmetry (20%), a decrease in ipsilateral striatal dopamine content (70%) and degeneration of dopamine neurons in the substantia nigra (70%). Chronic treatment with L-DOPA was administered for 35 days and consisted of three phases with incremental daily doses. The third phase resulted in 83-90% of rats developing severe abnormal involuntary movements (AIMs) which included limb and locomotive dyskinesia, axial dystonia and orolingual dyskinesia. Reproducibility of the model, criteria of strict blinding, placebo-controlled design, randomization of study subjects and pretrial determination of sample size were used to measure efficacy of amantadine and istradefylline and to validate the protocol design. Acute or subchronic post-treatment with amantadine reduced the severity of dyskinesia while istradefylline punctually attenuated AIMs. Our experimental conditions using gradual development of dyskinesia induced by increasing doses of <sub>L</sub>
-DOPA resulted in a reliable model of <sub>L</sub>
-DOPA-induced dyskinesia with a high rate of dyskinetic rats.</div>
</front>
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<fA06><s2>5</s2>
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<fA08 i1="01" i2="1" l="ENG"><s1>An improved model to investigate the efficacy of antidyskinetic agents in hemiparkinsonian rats</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>SPINNEWYN (Brigitte)</s1>
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<fA11 i1="02" i2="1"><s1>CHARNET (Christelle)</s1>
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<fA11 i1="03" i2="1"><s1>CORNET (Sylvie)</s1>
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<fA11 i1="04" i2="1"><s1>ROUBERT (Veronique)</s1>
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<fA11 i1="05" i2="1"><s1>CHABRIER (Pierre-Etienne)</s1>
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<fA11 i1="06" i2="1"><s1>AUGUET (Michel)</s1>
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<fA14 i1="01"><s1>Ipsen Innovation, 5 avenue du Canada</s1>
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<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
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<fC01 i1="01" l="ENG"><s0>A number of experimental models of <sub>L</sub>
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-DOPA-induced dyskinesia in rats to establish a reliable preclinical model. Two stereotaxic injections of 6-OHDA were administered in the left striatum. This model led to 90-100% of rats with a marked contralateral circling behaviour, significant limb use asymmetry (20%), a decrease in ipsilateral striatal dopamine content (70%) and degeneration of dopamine neurons in the substantia nigra (70%). Chronic treatment with L-DOPA was administered for 35 days and consisted of three phases with incremental daily doses. The third phase resulted in 83-90% of rats developing severe abnormal involuntary movements (AIMs) which included limb and locomotive dyskinesia, axial dystonia and orolingual dyskinesia. Reproducibility of the model, criteria of strict blinding, placebo-controlled design, randomization of study subjects and pretrial determination of sample size were used to measure efficacy of amantadine and istradefylline and to validate the protocol design. Acute or subchronic post-treatment with amantadine reduced the severity of dyskinesia while istradefylline punctually attenuated AIMs. Our experimental conditions using gradual development of dyskinesia induced by increasing doses of <sub>L</sub>
-DOPA resulted in a reliable model of <sub>L</sub>
-DOPA-induced dyskinesia with a high rate of dyskinetic rats.</s0>
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<fC03 i1="01" i2="X" l="FRE"><s0>Modèle</s0>
<s5>01</s5>
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<fC03 i1="01" i2="X" l="ENG"><s0>Models</s0>
<s5>01</s5>
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<fC03 i1="01" i2="X" l="SPA"><s0>Modelo</s0>
<s5>01</s5>
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<fC03 i1="02" i2="X" l="FRE"><s0>Efficacité traitement</s0>
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<s5>02</s5>
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<s5>03</s5>
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<fC03 i1="03" i2="X" l="ENG"><s0>Animal</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Animal</s0>
<s5>03</s5>
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<fC03 i1="04" i2="X" l="FRE"><s0>Rat</s0>
<s5>04</s5>
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<fC03 i1="04" i2="X" l="ENG"><s0>Rat</s0>
<s5>04</s5>
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<fC03 i1="04" i2="X" l="SPA"><s0>Rata</s0>
<s5>04</s5>
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<fC03 i1="05" i2="X" l="FRE"><s0>Oxidopamine</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>05</s5>
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<s2>NK</s2>
<s2>FR</s2>
<s5>05</s5>
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<fC03 i1="05" i2="X" l="SPA"><s0>Oxidopamina</s0>
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<s2>FR</s2>
<s5>05</s5>
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<s5>06</s5>
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<s5>06</s5>
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<s5>06</s5>
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<s2>FR</s2>
<s5>07</s5>
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<s2>NK</s2>
<s2>FR</s2>
<s5>07</s5>
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<fC03 i1="07" i2="X" l="SPA"><s0>Levodopa</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>07</s5>
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<fC03 i1="08" i2="X" l="FRE"><s0>Maladie de Parkinson</s0>
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<s5>08</s5>
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<s5>08</s5>
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<s5>23</s5>
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<s5>41</s5>
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<s5>42</s5>
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<s5>43</s5>
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<s5>44</s5>
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<s5>44</s5>
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<s5>45</s5>
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<s5>45</s5>
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<s5>45</s5>
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<s5>47</s5>
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<s5>47</s5>
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<s5>48</s5>
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<s5>48</s5>
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<s5>48</s5>
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<fN21><s1>290</s1>
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<server><NO>PASCAL 11-0418967 INIST</NO>
<ET>An improved model to investigate the efficacy of antidyskinetic agents in hemiparkinsonian rats</ET>
<AU>SPINNEWYN (Brigitte); CHARNET (Christelle); CORNET (Sylvie); ROUBERT (Veronique); CHABRIER (Pierre-Etienne); AUGUET (Michel)</AU>
<AF>Ipsen Innovation, 5 avenue du Canada/91940 Les Ulis/France (1 aut., 2 aut., 3 aut., 4 aut., 5 aut., 6 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Fundamental & clinical pharmacology; ISSN 0767-3981; Coden FCPHEZ; Royaume-Uni; Da. 2011; Vol. 25; No. 5; Pp. 608-618; Bibl. 43 ref.</SO>
<LA>Anglais</LA>
<EA>A number of experimental models of <sub>L</sub>
-DOPA-induced dyskinesia have been proposed, but these models result in a low to medium rate of dyskinetic animals with mild to severe symptoms. The objective of this study was to combine a model of 6-OHDA-induced parkinsonism and of <sub>L</sub>
-DOPA-induced dyskinesia in rats to establish a reliable preclinical model. Two stereotaxic injections of 6-OHDA were administered in the left striatum. This model led to 90-100% of rats with a marked contralateral circling behaviour, significant limb use asymmetry (20%), a decrease in ipsilateral striatal dopamine content (70%) and degeneration of dopamine neurons in the substantia nigra (70%). Chronic treatment with L-DOPA was administered for 35 days and consisted of three phases with incremental daily doses. The third phase resulted in 83-90% of rats developing severe abnormal involuntary movements (AIMs) which included limb and locomotive dyskinesia, axial dystonia and orolingual dyskinesia. Reproducibility of the model, criteria of strict blinding, placebo-controlled design, randomization of study subjects and pretrial determination of sample size were used to measure efficacy of amantadine and istradefylline and to validate the protocol design. Acute or subchronic post-treatment with amantadine reduced the severity of dyskinesia while istradefylline punctually attenuated AIMs. Our experimental conditions using gradual development of dyskinesia induced by increasing doses of <sub>L</sub>
-DOPA resulted in a reliable model of <sub>L</sub>
-DOPA-induced dyskinesia with a high rate of dyskinetic rats.</EA>
<CC>002B02; 002B17A01; 002B17G</CC>
<FD>Modèle; Efficacité traitement; Animal; Rat; Oxidopamine; Dyskinésie; Lévodopa; Maladie de Parkinson; Contrôle moteur</FD>
<FG>Rodentia; Mammalia; Vertebrata; Agoniste; Récepteur adrénergique; Sympathomimétique; Syndrome extrapyramidal; Mouvement involontaire; Pathologie du   système nerveux; Trouble neurologique; Récepteur dopaminergique D2; Antiparkinsonien; Maladie dégénérative; Pathologie de l'encéphale; Pathologie du   système nerveux central</FG>
<ED>Models; Treatment efficiency; Animal; Rat; Oxidopamine; Dyskinesia; Levodopa; Parkinson disease; Motor control</ED>
<EG>Rodentia; Mammalia; Vertebrata; Agonist; Adrenergic receptor; Sympathomimetic; Extrapyramidal syndrome; Involuntary movement; Nervous system diseases; Neurological disorder; D2 Dopamine receptor; Antiparkinson agent; Degenerative disease; Cerebral disorder; Central nervous system disease</EG>
<SD>Modelo; Eficacia tratamiento; Animal; Rata; Oxidopamina; Disquinesia; Levodopa; Parkinson enfermedad; Control motor</SD>
<LO>INIST-14711.354000191207660070</LO>
<ID>11-0418967</ID>
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	La maladie de Parkinson en France (serveur d'exploration)
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La maladie de Parkinson en France (serveur d'exploration)

An improved model to investigate the efficacy of antidyskinetic agents in hemiparkinsonian rats

An improved model to investigate the efficacy of antidyskinetic agents in hemiparkinsonian rats

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