The dopamine stabilizer (-)-OSU6162 attenuates levodopa-induced dyskinesia in the unilateral 6-hydroxydopamine rat model of Parkinson’s disease

Abstract

Levodopa-induced dyskinesia (LID) is a complication that occurs in many patients with Parkinson’s disease. (-)-OSU6162 is a clinically tolerable dopamine stabilizer with affinity for both dopaminergic D₂ receptors and serotonergic 5-HT_2A receptors which has been shown to counteract LID in non-human primates. To investigate whether (-)-OSU6162 can dampen levodopa-induced abnormal involuntary movements in the unilateral 6-OHDA rat model of Parkinson’s disease without impairing levodopa-induced improvement in motor functioning, female Sprague Dawley rats received complete unilateral lesioning of the medial forebrain bundle and were treated daily with levodopa/benserazide. Animals that developed dyskinetic behavior as assessed by involuntary abnormal movements following two weeks of treatment with levodopa/benserazide received either (-)-OSU6162 (30 mg/kg) or saline immediately prior to their next levodopa/benserazide dose. In a separate batch of animals, the same add-on treatment was given following three days of levodopa/benserazide administration prior to subjecting the animals to the stepping and cylinder tests. (-)-OSU6162 was found to significantly reduce levodopa-induced abnormal involuntary movements in dyskinetic rats without compromising the effect of levodopa in the stepping test. In conclusion, add-on of (-)-OSU6162 attenuates the expression of LID in the 6-OHDA rat model of Parkinson’s disease without affecting the antiparkinsonian effect of levodopa.