title: Generation of a model of L-DOPA-induced dyskinesia in two different mouse strains.
abstract: Prolonged use of the dopamine precursor L-DOPA for the treatment of Parkinson's disease commonly results in abnormal involuntary movements, which are termed L-DOPA-induced dyskinesia (LID). Over-activity at corticostriatal synapses onto neurons of the direct and indirect striatal output pathways has been implicated in the development of dyskinesia, but it has proved difficult to investigate the pathways separately due to their morphological similarities. The recent development of bacterial artificial chromosome mice that express green fluorescent protein in either the direct or indirect pathway allows visual identification of the output neurons in each pathway. Here we describe the use of two different strains of these transgenic mice (pure FVB and FVB crossed with C57BL6) in the development of mouse models of L-DOPA-induced dyskinesia. This model will allow the direct and indirect pathways to be studied individually to delineate the cellular and molecular mechanisms underlying dyskinesias. These studies demonstrate that mouse strain impacts on behavioural responses and L-DOPA sensitivity. Therefore, when generating mouse models of LID, strain must be taken into consideration when choosing the L-DOPA dosing regimen.
authors.affiliation: Centre for Neurobiology of Stress, Dept Biological Sciences, University of Toronto at Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada. sthiele@utsc.utoronto.ca
authors.forename: Sherri L
authors.initials: SL
authors.lastname: Thiele
authors.forename: Ruth
authors.initials: R
authors.lastname: Warre
authors.forename: Charline S
authors.initials: CS
authors.lastname: Khademullah
authors.forename: Nusrat
authors.initials: N
authors.lastname: Fahana
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lo
authors.forename: Doris
authors.initials: D
authors.lastname: Lam
authors.forename: Sheena
authors.initials: S
authors.lastname: Talwar
authors.forename: Tom H
authors.initials: TH
authors.lastname: Johnston
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Brotchie
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Nash
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000209:etiology* / Q000235:genetics; D004525:Efferent Pathways / Q000187:drug effects / Q000503:physiopathology; D007980:Levodopa / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa