[Abstract Title]. - Society for Neuroscience

Disclosures: T. Kimura, None; K. Kannari , None; M. Tomiyama, None; A. Arai, None; M.
Shouji, None.
Poster
247. Parkinson's Disease Interventions: Animal and Clinical Models
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 247.24/T7
Topic: C.02.d. Therapies
Support: Solvay Pharmaceuticals Research Laboratories
Title: Differential expression of abnormal involuntary movements with short and long acting
dopamine receptor agonists in levodopa treated and untreated 6-hydroxydopamine-lesioned rats
Authors: *M. PAPATHANOU 1 , A. MCCREARY 2 , S. ROSE 1 , P. JENNER 1 ;
1 NDRG, King's Col. London, London, United Kingdom; 2 Solvay Pharmaceuticals Res. Labs.,
Weesp, Netherlands
Abstract: Long term L-3,4-dihydroxyphenylalanine (L-Dopa) treatment in Parkinson‟s disease
results in the expression of abnormal involuntary movements (AIMs) or dyskinesia. The severity
of dyskinesia may be related to the duration of dopaminergic stimulation. In L-Dopa primed and
drug naïve (unprimed) non-human primates continuous dopaminergic stimulation with long
acting dopamine receptor agonists (DRAs) produces less severe dyskinesia than intermittent
stimulation with short acting DRAs or L-Dopa (Maratos et al., 2003). Whether this differential
effect is also seen in 6-hydroxydopamine (6-OHDA)-lesioned rats is not known and is the
purpose of this study.
Male Wistar rats were lesioned with 6-OHDA in the medial forebrain bundle. Rats in Group 1
(n=24) were primed to induce AIMs with L-Dopa (6.25mg/kg + benserazide 15mg/kg i.p. s.i.d.)
(LD/B) for 3 weeks followed by LD/B and the short acting DRAs apomorphine (0.0625mg/kg
s.c.) and ropinirole (0.4mg/kg s.c.) (n=12) or LD/B and the long acting DRAs pramipexole
(0.0375mg/kg s.c.) and pergolide (0.03125mg/kg s.c.) (n=12) in a cross over design. Group 2
(n=36) was divided into 6 groups (n=6) and treated with saline, LD/B, apomorphine, ropinirole,
pramipexole or pergolide for 3 weeks. In both groups AIMs was assessed (scale from 0-4)
(Carlsson et al., 2005) for up to 6 hours after drug administration. The above doses of the DRAs
showed similar total number of rotations at peak activity as LD/B, obtained previously with
rotometry.
In L-Dopa primed animals (group 1) LD/B induced maximum AIMs scores at peak activity, with
an overall duration of activity of 210 mins. Similarly apomorphine and ropinirole expressed
maximum peak AIMs scores with a duration of activity 135 and 150 mins respectively. In