Pramipexole reverses Parkinson's disease-related motivational deficits in rats.
Identifieur interne : 000473 ( Main/Exploration ); précédent : 000472; suivant : 000474Pramipexole reverses Parkinson's disease-related motivational deficits in rats.
Auteurs : Mathieu Favier [France] ; Theo Duran ; Carole Carcenac ; Guillaume Drui ; Marc Savasta ; Sebastien CarnicellaSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2014.
English descriptors
- KwdEn :
- MESH :
- chemical , drug effects : Receptors, Dopamine.
- chemical , metabolism : Dopamine.
- chemical , therapeutic use : Benzothiazoles, Dopamine Agonists.
- drug effects : Apathy, Behavior, Animal, Brain.
- drug therapy : Parkinson Disease.
- Animals, Disease Models, Animal, Rats.
Abstract
Recent evidence suggests that Parkinson's disease affects not only movement, but also cognitive and psychiatric functions. Among these nonmotor complications, apathy, which is defined as a lack of motivation and operationalized as a quantitative reduction in goal-directed behavior, may even precede motor impairments, disappearing with the introduction of dopaminergic (DA) therapies and possibly reappearing with its discontinuation, suggesting a causal role of DA. We recently developed a lesion-based model, with stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into precise areas of the rat SNc or ventral tegmental area and showed, in several operant tasks, that a partial denervation of the nigrostriatal, but not of the mesocorticolimbic, DA system induced profound motivational deficits during instrumental action. We investigated the time course of the effects of nigrostriatal DA denervation on motivation in rats, by assessing the negative effect of SNc bilateral 6-OHDA infusion on preacquired operant behavior, and determining whether the induced deficits were sensitive to the introduction and withdrawal of a clinically relevant PD treatment, the DA D2/D3 receptor agonist, pramipexole (PRA). Partial nigrostriatal DA denervation was accompanied by a significant reduction in operant behavior. This deficit, indicative of a decrease in motivation, was fully reversed by PRA and reappeared after treatment withdrawal. This longitudinal preclinical study provides evidence for the implication of the DA nigrostriatal system in PD-associated apathy. Moreover, by showing a good isomorphy and predictive value, our model highlights the relevance of D2/D3 receptors as potential targets for alleviating apathy in PD.
DOI: 10.1002/mds.25837
PubMed: 24515412
Affiliations:
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Université Joseph Fourier, Grenoble, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institute of Neuroscience, Dynamic and Pathophysiology of Basal Ganglia, Grenoble, France; Université Joseph Fourier, Grenoble</wicri:regionArea><placeName><settlement type="city">Grenoble</settlement></placeName><orgName type="university">Université Joseph Fourier</orgName><placeName><settlement type="city">Grenoble</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName></affiliation></author><author><name sortKey="Duran, Theo" sort="Duran, Theo" uniqKey="Duran T" first="Theo" last="Duran">Theo Duran</name></author><author><name sortKey="Carcenac, Carole" sort="Carcenac, Carole" uniqKey="Carcenac C" first="Carole" last="Carcenac">Carole Carcenac</name></author><author><name sortKey="Drui, Guillaume" sort="Drui, Guillaume" uniqKey="Drui G" first="Guillaume" last="Drui">Guillaume Drui</name></author><author><name sortKey="Savasta, Marc" sort="Savasta, Marc" uniqKey="Savasta M" first="Marc" last="Savasta">Marc Savasta</name></author><author><name sortKey="Carnicella, Sebastien" sort="Carnicella, Sebastien" uniqKey="Carnicella S" first="Sebastien" last="Carnicella">Sebastien Carnicella</name></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="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Apathy (drug effects)</term><term>Behavior, Animal (drug effects)</term><term>Benzothiazoles (therapeutic use)</term><term>Brain (drug effects)</term><term>Disease Models, Animal</term><term>Dopamine (metabolism)</term><term>Dopamine Agonists (therapeutic use)</term><term>Parkinson Disease (drug therapy)</term><term>Rats</term><term>Receptors, Dopamine (drug effects)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Receptors, Dopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Benzothiazoles</term><term>Dopamine Agonists</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apathy</term><term>Behavior, Animal</term><term>Brain</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Rats</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Recent evidence suggests that Parkinson's disease affects not only movement, but also cognitive and psychiatric functions. Among these nonmotor complications, apathy, which is defined as a lack of motivation and operationalized as a quantitative reduction in goal-directed behavior, may even precede motor impairments, disappearing with the introduction of dopaminergic (DA) therapies and possibly reappearing with its discontinuation, suggesting a causal role of DA. We recently developed a lesion-based model, with stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into precise areas of the rat SNc or ventral tegmental area and showed, in several operant tasks, that a partial denervation of the nigrostriatal, but not of the mesocorticolimbic, DA system induced profound motivational deficits during instrumental action. We investigated the time course of the effects of nigrostriatal DA denervation on motivation in rats, by assessing the negative effect of SNc bilateral 6-OHDA infusion on preacquired operant behavior, and determining whether the induced deficits were sensitive to the introduction and withdrawal of a clinically relevant PD treatment, the DA D2/D3 receptor agonist, pramipexole (PRA). Partial nigrostriatal DA denervation was accompanied by a significant reduction in operant behavior. This deficit, indicative of a decrease in motivation, was fully reversed by PRA and reappeared after treatment withdrawal. This longitudinal preclinical study provides evidence for the implication of the DA nigrostriatal system in PD-associated apathy. Moreover, by showing a good isomorphy and predictive value, our model highlights the relevance of D2/D3 receptors as potential targets for alleviating apathy in PD.</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><orgName><li>Université Joseph Fourier</li></orgName></list><tree><noCountry><name sortKey="Carcenac, Carole" sort="Carcenac, Carole" uniqKey="Carcenac C" first="Carole" last="Carcenac">Carole Carcenac</name><name sortKey="Carnicella, Sebastien" sort="Carnicella, Sebastien" uniqKey="Carnicella S" first="Sebastien" last="Carnicella">Sebastien Carnicella</name><name sortKey="Drui, Guillaume" sort="Drui, Guillaume" uniqKey="Drui G" first="Guillaume" last="Drui">Guillaume Drui</name><name sortKey="Duran, Theo" sort="Duran, Theo" uniqKey="Duran T" first="Theo" last="Duran">Theo Duran</name><name sortKey="Savasta, Marc" sort="Savasta, Marc" uniqKey="Savasta M" first="Marc" last="Savasta">Marc Savasta</name></noCountry><country name="France"><noRegion><name sortKey="Favier, Mathieu" sort="Favier, Mathieu" uniqKey="Favier M" first="Mathieu" last="Favier">Mathieu Favier</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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