[Abstract Title]. - Society for Neuroscience

Unilateral intrastriatal injection of 6-hydroxydopamine (2x6µg) in rats was chosen as a model of
parkinson‟s disease. Four weeks later, administration of escalating doses of L-DOPA during 4
weeks led to AIMs in the majority of rats. Thus, we have examined the effect of acute or
subchronic treatment with BN82451 (from 1 to 30 mg/kg; p.o.) on L-DOPA-induced locomotive,
axial, orolingual and forelimb dyskinesia. For acute treatment, BN82451 was administered just
after the first AIM measurement (30 minutes after L-DOPA injection) and for subchronic
determination, treatment was pursued the 4 consecutive days, twice a day according to its
pharmacokinetics and AIMs were measured at Day 1 and Day 5. Plasma L-DOPA, striatal
dopamine were not affected by BN82451 administration at 10 mg/kg; p.o.
BN82451 markedly and dose dependently reduced the severity of dyskinesia. The results also
show that a single administration of BN82451 alleviates dyskinesia induced by L-DOPA in
hemiparkinsonian rats and demonstrate that subchronic treatments necessitate lower doses to
achieve the same antidyskinetic efficacy.
This protocol, using gradual development of dyskinesia induced by increasing doses of L-DOPA
result in a sound model of L-DOPA induced dyskinesia with a high rate of dyskinetic rats. In
these experimental conditions, BN82451 reduces AIMs and might represent a treatment option
for managing dyskinesia in PD.
Disclosures: P.E. Chabrier , IPSEN, A. Employment (full or part-time); B. Spinnewyn,
IPSEN, A. Employment (full or part-time); C. Charnet, IPSEN, A. Employment (full or parttime);
S. Bernetiere, IPSEN, A. Employment (full or part-time); P. Roubert, IPSEN, A.
Employment (full or part-time); L. Vignaux, IPSEN, A. Employment (full or part-time); J.
Camara, IPSEN, A. Employment (full or part-time); M. Auguet, IPSEN, A. Employment (full
or part-time).
Poster
247. Parkinson's Disease Interventions: Animal and Clinical Models
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 247.27/T10
Topic: C.02.d. Therapies
Title: New treatment (BN82451) and assessment for L-Dopa-induced dyskinesias in
parkinsonian macaques
Authors: *R. ARON BADIN 1,2 , E. BROUILLET 1,2 , B. SPINNEWYN 3 , M. AUGUET 3 , P.-E.
CHABRIER 3 , P. HANTRAYE 1 ;
1 Molec Imag Res. Center(MIRCen), CEA,Inst Biomed Imaging (I2BM), Fontenay aux Roses,
France; 2 CNRS, URA 2210, Orsay, France; 3 IPSEN, Inst. Henri Beaufour, Les Ulis, France