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dc.contributor.authorIravani, Mahmoud M.
dc.contributor.authorTayarani-Binazir, Kayhan
dc.contributor.authorChu, Wing B.
dc.contributor.authorJackson, Michael J.
dc.contributor.authorJenner, Peter
dc.date.accessioned2013-12-17T13:30:12Z
dc.date.available2013-12-17T13:30:12Z
dc.date.issued2006-12
dc.identifier.citationIravani , M M , Tayarani-Binazir , K , Chu , W B , Jackson , M J & Jenner , P 2006 , ' In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates, the selective 5-hydroxytryptamine 1a agonist (R)-(+)-8-OHDPAT inhibits levodopa-induced dyskinesia but only with\increased motor disability ' , Journal of Pharmacology and Experimental Therapeutics , vol. 319 , no. 3 , pp. 1225-1234 . https://doi.org/10.1124/jpet.106.110429
dc.identifier.issn0022-3565
dc.identifier.otherPURE: 735200
dc.identifier.otherPURE UUID: e6385b61-e558-499a-a9ee-241af98d95da
dc.identifier.otherWOS: 000242048500026
dc.identifier.otherScopus: 33751167879
dc.identifier.urihttp://hdl.handle.net/2299/12374
dc.description.abstract5-Hydroxytryptamine 1a (5-HT1a) receptor agonists, such as sarizotan and tandospirone, are reported to reduce levodopainduced dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques and in Parkinson's disease without worsening motor disability. However, these compounds are not specific for 5-HT1a receptors and also possess dopamine antagonist actions. We now report on the effects of (2R)-(+)-8-hydroxy-2-(di-n-propylamino) tetralin [(R)-(+)-8-OHDPAT], a selective 5-HT1a agonist lacking dopaminergic activity, on motor disability and dyskinesia (chorea and dystonia) in levodopa-primed MPTP-treated common marmosets. Administration of (R)-(+)-8-OHDPAT (0.2, 0.6, and 2.0 mg/ kg s.c), in conjunction with levodopa/ carbidopa (12.5 mg/ kg each p.o.) to levodopa-primed animals, dose-dependently reduced levodopa-induced chorea but did not affect dystonic movements. However, (R)-(+)-8-OHDPAT treatment also reduced locomotor activity and the reversal of motor disability. Administration of (R)-(+)-8-OHDPAT alone had no effects of motor behaviors. The effects of (R)-(+)-8-OHDPAT on levodopa-induced motor behaviors were antagonized by the 5-HT1a receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]N-2-pyridinylcyclohexanecarboxamide maleate (WAY-100635) (1.0 mg/ kg s. c.). Administration of (R)-(+)-8-OHDPAT (0.6 mg/ kg s. c.) also reduced chorea produced by the administration of the D-2/D-3 dopamine receptor agonist pramipexole (0.06 mg/ kg p. o.) to levodopa-primed MPTP-treated animals. However, again the increase in locomotor activity and reversal of motor disability produced by pramipexole were also inhibited. These data suggest that selective 5-HT1a agonists do not provide an effective means of suppressing levodopa-induced dyskinesia, except with worsening of parkinsonism.en
dc.format.extent10
dc.language.isoeng
dc.relation.ispartofJournal of Pharmacology and Experimental Therapeutics
dc.subject5-HT1A RECEPTOR AGONIST
dc.subjectSTRIATAL DOPAMINE RELEASE
dc.subjectPARKINSONS-DISEASE
dc.subjectRAT STRIATUM
dc.subjectIN-VIVO
dc.subject8-OH-DPAT
dc.subjectSARIZOTAN
dc.subjectBRAIN
dc.subjectANTAGONISTS
dc.subjectEXPRESSION
dc.titleIn 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates, the selective 5-hydroxytryptamine 1a agonist (R)-(+)-8-OHDPAT inhibits levodopa-induced dyskinesia but only with\increased motor disabilityen
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionPharmacology and Clinical Science Research
dc.contributor.institutionNeurodegenerative Diseases
dc.contributor.institutionAgriculture, Veterinary and Food Sciences
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
rioxxterms.versionofrecordhttps://doi.org/10.1124/jpet.106.110429
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstyperestrictedAccess


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