Reversal of reserpine‐induced catalepsy by selective D1 and D2 dopamine agonists
Identifieur interne : 000F75 ( Istex/Curation ); précédent : 000F74; suivant : 000F76Reversal of reserpine‐induced catalepsy by selective D1 and D2 dopamine agonists
Auteurs : C. Anthony Hubbard [États-Unis] ; Trugman [États-Unis]Source :
- Movement Disorders [ 0885-3185 ] ; 1993.
English descriptors
Abstract
To gain insight into the antiparkinsonian effects of selective D1 and D2 dopamine receptor stimulation, we examined the ability of D1 (SKF 38393) and D2 (quinpirole) agonists to reverse catalepsy induced by the combined administration of reserpine and α‐methyl‐p‐tyrosine (AMPT) in rats. Catalepsy, the failure to correct an externally imposed posture, is a measure of akinesia and was assessed using the bar test. Rats injected with reserpine alone (2.5 mg/ kg i.p.) developed akinesia and ptosis within 60‐90 min. The D1 agonist SKF 38393 (30 mg/ kg i.v.) rapidly reversed ptosis and restored near‐normal mobility when administered 24 h after reserpine and AMPT; catalepsy was reversed for 90 min, after which the drug effect wore off. Quinpirole (1 mg/ kg i.v.) reversed catalepsy for the duration of the test period (4 h) but did not consistently reverse ptosis or promote normal mobility; the rats continued to exhibit kyphotic postures with little spontaneous locomotion. These results indicate that selective D1 stimulation is sufficient to reverse reserpine‐induced akinesia and highlight the need for the development of potent selective D1 agonists for clincal traial in Parkinson's disease. In serve dopamine depletion, D2 stimulation alone appears to be insufficient to restore normal movement. Quinpirole, but not SKF 38393, elicited paroxysmal limb/ body jerking in reserpine‐AMPT‐treated rats, providing further evidence that atypical jerking can be elicited by D2 stimulation in the complete absence of D1 stimulation. This laboratory observation suggests that some jerking dyskinesias seen in treated parkinsonian patients may be mediated by an imbalance in D1‐D2 receptor stimulation.
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DOI: 10.1002/mds.870080410
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Anthony Hubbard</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, University of Virginia Health Sciences Center, Charlottesville, Virginia, U.S.A.</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Virginia Health Sciences Center, Charlottesville, Virginia</wicri:regionArea></affiliation></author><author><name sortKey="Trugman" sort="Trugman" uniqKey="Trugman" last="Trugman">Trugman</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, University of Virginia Health Sciences Center, Charlottesville, Virginia, U.S.A.</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Virginia Health Sciences Center, Charlottesville, Virginia</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:A3A8C0823B3FB678772FBBB4AE1D70BADB8CADA2</idno><date when="1993" year="1993">1993</date><idno type="doi">10.1002/mds.870080410</idno><idno type="url">https://api.istex.fr/document/A3A8C0823B3FB678772FBBB4AE1D70BADB8CADA2/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000F75</idno><idno type="wicri:Area/Istex/Curation">000F75</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Reversal of reserpine‐induced catalepsy by selective D1 and D2 dopamine agonists</title><author><name sortKey="Hubbard, C Anthony" sort="Hubbard, C Anthony" uniqKey="Hubbard C" first="C. Anthony" last="Hubbard">C. Anthony Hubbard</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, University of Virginia Health Sciences Center, Charlottesville, Virginia, U.S.A.</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Virginia Health Sciences Center, Charlottesville, Virginia</wicri:regionArea></affiliation></author><author><name sortKey="Trugman" sort="Trugman" uniqKey="Trugman" last="Trugman">Trugman</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, University of Virginia Health Sciences Center, Charlottesville, Virginia, U.S.A.</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Virginia Health Sciences Center, Charlottesville, Virginia</wicri:regionArea></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="sub">Official Journal of the Movement Disorder Society</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="1993">1993</date><biblScope unit="vol">8</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="473">473</biblScope><biblScope unit="page" to="478">478</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">A3A8C0823B3FB678772FBBB4AE1D70BADB8CADA2</idno><idno type="DOI">10.1002/mds.870080410</idno><idno type="ArticleID">MDS870080410</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Catalepsy</term><term>D1 and D2 dopamine agonist</term><term>Parkinsonism</term><term>Rat</term><term>Reserpine</term><term>α‐Methyl‐p‐tyrosine</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">To gain insight into the antiparkinsonian effects of selective D1 and D2 dopamine receptor stimulation, we examined the ability of D1 (SKF 38393) and D2 (quinpirole) agonists to reverse catalepsy induced by the combined administration of reserpine and α‐methyl‐p‐tyrosine (AMPT) in rats. Catalepsy, the failure to correct an externally imposed posture, is a measure of akinesia and was assessed using the bar test. Rats injected with reserpine alone (2.5 mg/ kg i.p.) developed akinesia and ptosis within 60‐90 min. The D1 agonist SKF 38393 (30 mg/ kg i.v.) rapidly reversed ptosis and restored near‐normal mobility when administered 24 h after reserpine and AMPT; catalepsy was reversed for 90 min, after which the drug effect wore off. Quinpirole (1 mg/ kg i.v.) reversed catalepsy for the duration of the test period (4 h) but did not consistently reverse ptosis or promote normal mobility; the rats continued to exhibit kyphotic postures with little spontaneous locomotion. These results indicate that selective D1 stimulation is sufficient to reverse reserpine‐induced akinesia and highlight the need for the development of potent selective D1 agonists for clincal traial in Parkinson's disease. In serve dopamine depletion, D2 stimulation alone appears to be insufficient to restore normal movement. Quinpirole, but not SKF 38393, elicited paroxysmal limb/ body jerking in reserpine‐AMPT‐treated rats, providing further evidence that atypical jerking can be elicited by D2 stimulation in the complete absence of D1 stimulation. This laboratory observation suggests that some jerking dyskinesias seen in treated parkinsonian patients may be mediated by an imbalance in D1‐D2 receptor stimulation.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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