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Induction and expression of abnormal involuntary movements is related to the duration of dopaminergic stimulation in 6-OHDA-lesioned rats
(Neurodegenerative Disease Research Group, School of Biomedical Sciences, King s College, Southwark, London SE1 8UB, UK)
(Neurodegenerative Disease Research Group, School of Biomedical Sciences, King s College, Southwark, London SE1 8UB, UK)
(Abbott Healthcare B.V, C J Van Houtenlaan 36, Weesp, The Netherlands)
(Neurodegenerative Disease Research Group, School of Biomedical Sciences, King s College, Southwark, London SE1 8UB, UK)
2011 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 33, no 12, 2247-2254 p.Article in journal (Refereed) Published
Abstract [en]

Dyskinesia induction in Parkinson’s disease (PD) appears less marked with long-acting dopamine agonists than with short-acting L-Dopa, but the relationship to duration of drug action is unknown. It is also unclear whether the duration of drug action affects the expression of established dyskinesia. This study compared the ability of L-Dopa and four dopamine agonists of different duration of action to induce abnormal involuntary movements (AIMs) in 6-hydroxydopamine (6-OHDA)-lesioned rats, and their ability to express established AIMs following prior exposure to L-Dopa. 6-OHDA-lesioned rats were treated with saline, L-Dopa/benserazide, apomorphine, ropinirole, pramipexole or pergolide once daily for 15 days. Repeated administration of the short-acting dopamine agonists, apomorphine (duration 80 min) and ropinirole (duration 90 min) induced marked axial, limb and orolingual AIMs at peak effect. L-Dopa (duration 100 min) produced moderate AIMs at peak effect, while administration of the long-acting dopamine agonists, pramipexole (duration 150 min) and pergolide (duration 240 min) resulted in mild AIMs. In rats primed to exhibit severe AIMs following repeated L-Dopa administration, acute administration of apomorphine, ropinirole and L-Dopa induced severe AIMs. By contrast, pramipexole and pergolide evoked only mild–moderate AIMs. Again, there was a negative correlation between duration of effect and the severity of AIMs expressed. These studies show that both the induction and expression of AIMs in 6-OHDA-lesioned rats are related to the duration of action of dopaminergic drugs. These findings suggest that continuous dopaminergic stimulation could be used both to avoid dyskinesia induction and to improve motor function in late-stage PD when troublesome dyskinesia is evident.

Place, publisher, year, edition, pages
2011. Vol. 33, no 12, 2247-2254 p.
Keyword [en]
abnormal involuntary movements;continuous dopaminergic stimulation;dopamine agonists;L-Dopa;Parkinson’s disease
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-287787DOI: 10.1111/j.1460-9568.2011.07704.xOAI: oai:DiVA.org:uu-287787DiVA: diva2:923454
Available from: 2016-04-26 Created: 2016-04-26 Last updated: 2016-05-16Bibliographically approved

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