title: Transcriptional alterations under continuous or pulsatile dopaminergic treatment in dyskinetic rats.
abstract: Continuous dopaminergic treatment is considered to prevent or delay the occurrence of dyskinesia in patients with Parkinson's disease (PD). Rotigotine is a non-ergolinic D(3) > D(2) > D(1) dopamine-receptor agonist for the treatment of PD using a transdermal delivery system providing stable plasma levels. We aimed to investigate the differential influence on gene expression of pulsatile L: -DOPA or rotigotine versus a continuous rotigotine treatment. The gene expression profile within the nigro-striatal system of unilateral 6-hydroxydopamine-lesioned rats was assessed in order to differentiate potential changes in gene expression following the various treatment using Affymetrix microarrays and quantitative RT-PCR. The expression of 15 genes in the substantia nigra and of 11 genes in the striatum was altered under pulsatile treatments inducing dyskinetic motor response, but was unchanged under continuous rotigotine treatment that did not cause dyskinetic motor response. The route of administration of a dopaminergic drug is important for the induction or prevention of motor abnormalities and adaptive gene expressions. The decline of neurotrophin-3 expression under pulsatile administration was considered of particular importance.
authors.affiliation: Neurochemistry Laboratory, Department of Psychiatry, Psychosomatics and Psychotherapy, National Parkinson Foundation Centre of Excellence Laboratories, University of Würzburg, Würzburg, Germany. edna.gruenblatt@kjpdzh.ch
authors.forename: E
authors.initials: E
authors.lastname: Grünblatt
authors.forename: W J
authors.initials: WJ
authors.lastname: Schmidt
authors.forename: D K A
authors.initials: DK
authors.lastname: Scheller
authors.forename: P
authors.initials: P
authors.lastname: Riederer
authors.forename: M
authors.initials: M
authors.lastname: Gerlach
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000008:administration & dosage*; D004409:Dyskinesia, Drug-Induced / Q000473:pathology*; D007839:Functional Laterality; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D007980:Levodopa / Q000008:administration & dosage*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy; D011673:Pulsatile Flow; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015259:Dopamine Agents; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D012333:RNA, Messenger; D007980:Levodopa; D016627:Oxidopamine