title: Levodopa infusion does not decrease the onset of abnormal involuntary movements in parkinsonian rats.
abstract: The short duration of effect of levodopa is linked to pulsatile stimulation of striatal dopamine receptors and dyskinesia induction. However, the recent introduction of intraduodenal (i.d.) infusions and novel oral controlled release formulations of l-dopa may prevent dyskinesia induction and reduce the severity of established involuntary movements. We have compared the effects of twice-daily intraperitoneal (i.p.) administration and daily i.d. infusion of l-dopa on the induction and expression of abnormal involuntary movements in 6-hydroxydopamine (6-OHDA)-lesioned rats. Animals were treated with either twice-daily i.p. administration of l-dopa/carbidopa (7.85/12.5 mg/kg) or an 8-hour i.d. infusion of l-dopa/carbidopa (20/5 mg/mL; infusion rate: 0.04 mL/h) for 14 days, after which treatments were switched between groups and continued for a further 14 days. Pulsatile i.p. administration of l-dopa induced moderate to severe abnormal involuntary movements, which gradually increased in severity over the 14 days, but i.d. infusion of l-dopa induced abnormal involuntary movements of a similar severity. Switching from continuous i.d. to pulsatile i.p. administration of l-dopa continued to provoke severe abnormal involuntary movements expression. Switching from pulsatile i.p. to continuous i.d. l-dopa administration did not alter the peak abnormal involuntary movement severity but tended to reduce their duration. Treatment with less pulsatile l-dopa administration using i.d. infusion does not reduce the risk of the appearance of dyskinesia. By contrast, the duration of established dyskinesia can be reduced by more continuous l-dopa delivery in agreement with clinical experience.
authors.affiliation: Abbott Healthcare Products B.V., Weesp, the Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Papathanou
authors.forename: Rika
authors.initials: R
authors.lastname: van der Laan
authors.forename: Peter
authors.initials: P
authors.lastname: Jenner
authors.forename: Sarah
authors.initials: S
authors.lastname: Rose
authors.forename: Andrew C
authors.initials: AC
authors.lastname: McCreary
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D004195:Disease Models, Animal; D020820:Dyskinesias / Q000188:drug therapy* / Q000209:etiology; D007980:Levodopa / Q000008:administration & dosage*; D008297:Male; D008474:Medial Forebrain Bundle / Q000293:injuries; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D007980:Levodopa; D016627:Oxidopamine
keywords: 6-OHDA-lesioned rats; AIMs; Parkinson's disease; dyskinesia; intraduodenal levodopa infusion