Positive association between striatal serotonin level and abnormal involuntary movements in chronic L-DOPA-treated hemiparkinsonian rats

Abstract

Although L-DOPA represents the standard of care in Parkinson's disease, long-term treatment may be compromised by L-DOPA-induced dyskinesia (LID), with adverse fluctuations in motor responsiveness and progressive loss of control. Here we show that in rats with 6-hydroxydopamine-induced lesions of the median forebrain bundle, LID correlates with 5-HT levels. Rats were treated with L-DOPA (6 mg/kg) and benserazide (15 mg/kg) daily for 3 weeks to induce the development of abnormal involuntary movements (AIMS). After this chronic L-DOPA treatment, the lesion side of the rats displayed significant changes in striatal dopamine (DA) and 5-HT levels. Striatal DA and 5-hydroxytryptamine (5-HT) levels were inversely correlated, and AIMs were strongly positively correlated DA levels and negatively correlated with 5-HT levels. Axial AIMs were more strongly correlated with DA and 5-HT levels than were the other AIMs subtypes, while locomotive AIMs showed no significant correlation at all. In addition, striatal 5-HT was more strongly (negatively) correlated with the AIMs than striatal DA levels. These results demonstrate that 5-HT contributes to LID and that both striata DA (positively) and 5-HT(negatively) affect the severity of LID. We suggest that by strategic modification of the serotonin system it may be posible to attenuate the adverse effect of chronic L-DOPA therapy.