title: Investigating the molecular mechanisms of L-DOPA-induced dyskinesia in the mouse.
abstract: L-DOPA-induced dyskinesia (LID) is a major complication of the pharmacotherapy of Parkinson's disease (PD). Animal models of LID are essential for investigating pathogenic pathways and therapeutic targets. While non-human primates have been the preferred species for pathophysiological studies, mouse models of LID have been recently produced and characterized to facilitate molecular investigations. Most of these studies have used mice with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal projection sustaining treatment with L-DOPA for 1-4 weeks. Mice with complete medial forebrain bundle lesions have been found to develop dyskinetic movements of maximal severity associated with a pronounced post-synaptic supersensitivity of D1-receptor dependent signaling pathways throughout the striatum. In contrast, mice with striatal 6-OHDA lesions have been found to exhibit a variable susceptibility to LID and a regionally restricted post-synaptic supersensitivity. Genetic mouse models of PD have just started to be used for studies of LID, providing an opportunity to dissect the impact of genetic factors on the maladaptive neuroplasticity that drives the development of treatment-induced involuntary movements in PD.
authors.affiliation: Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, BMC F11, Sölvegatan 19, 22184 Lund, Sweden.
authors.forename: Veronica
authors.initials: V
authors.lastname: Francardo
authors.forename: M Angela
authors.initials: MA
authors.lastname: Cenci
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007980:Levodopa / Q000009:adverse effects; D051379:Mice; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D007980:Levodopa; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase
keywords: Animal models; Dopamine replacement therapy; Genetic models; Motor complications; Striatum