title: 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 with 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 striatal DA (positively) and 5-HT (negatively) affect the severity of LID. We suggest that by strategic modification of the serotonin system it may be possible to attenuate the adverse effects of chronic l-DOPA therapy.
authors.affiliation: Department of Pharmacology, College of Medicine, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Suk J
authors.initials: SJ
authors.lastname: Gil
authors.forename: Chang H
authors.initials: CH
authors.lastname: Park
authors.forename: Jeong E
authors.initials: JE
authors.lastname: Lee
authors.forename: Yang K
authors.initials: YK
authors.lastname: Minn
authors.forename: Hyun C
authors.initials: HC
authors.lastname: Koh
mesh_terms: D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism* / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D005260:Female; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000473:pathology; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*
chemical_list: D015259:Dopamine Agents; D012701:Serotonin; D007980:Levodopa; D001545:Benserazide; D016627:Oxidopamine; D004298:Dopamine