Premium
Chronic L‐DOPA treatment decreases striatal cannabinoid CB‐1 mRNA expression in MPTP‐treated marmosets
Author(s) -
Tel Banu C,
Pearce Ronald RK,
Rose Sarah,
Jenner Peter
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb87-d
In Basal Ganglia, cannabinoid CB1 receptor (CB1r) transmission plays an important role in altering motor functions. However, the function of CB1r in Parkinson’s disease (PD) or its treatment’s motor complications such as L‐DOPA‐induced dyskinesias is not well understood. We now report the effect of repeated oral treatment of MPTP‐treated common marmosets with L‐DOPA plus carbidopa (12.5 mg/kg plus 12.5 mg/kg), bromocriptine (0.5 mg/kg) and ropinirole (0.5 mg/kg) for 30 days on cannabinoid CB1r mRNAs expression in the brain slices using in situ hybridisation histochemistry. All drug treatments improved motor function, but L‐DOPA rapidly induced marked dyskinesia whereas bromocriptine and ropinirole induced only mild dyskinesia. MPTP treatment increased cannabinoid CB1r mRNA expression in caudate nucleus and putamen (p<0.05, Newman Keul’s test) although had no effect on nucleus accumbens. L‐DOPA administration reversed the increase in CB1r mRNA expression in putamen (p<0.05) however, further decreased the CB1r mRNA levels in caudate nucleus (p<0.05) and nucleus accumbens (p<0.05). Bromocriptine and ropinirole treatments had no effect on the increase in CB1r mRNA expression. The decrease in striatal CB1r mRNA levels induced by L‐DOPA administration may explain the motor complications occurring on long term treatment of PD. This study is supported by National Parkinson’s Foundation USA and Parkinson’s Disease Society UK.