title: Striatal plasticity in Parkinson's disease and L-dopa induced dyskinesia.
abstract: Striatal function adapts to the loss of nigrostriatal dopaminergic input in Parkinson's disease (PD) to initially maintain voluntary movement, but subsequently changes in response to drug treatment leading to the onset of motor complications, notably dyskinesia. Alterations in presynaptic dopaminergic function coupled to changes in the response of post-synaptic dopaminergic receptors causing alterations in striatal output underlie attempts at compensation and the control of movement in early PD. However, eventually compensation fails and persistent changes in striatal function ensue that involve morphological, biochemical and electrophysiological change. Key alterations occur in cholinergic and glutamatergic transmission in the striatum and there are changes in motor programming controlled by events involving LTP/LTD. Dopamine replacement therapy with L-dopa modifies altered striatal function and restores motor function but non-physiological dopamine receptor stimulation leads to altered signalling through D1 and D2 receptor systems and changes in striatal function causing abnormalities of LTP/LTD mediated through glutamatergic/nitric oxide (NO) mechanisms. These lead to the onset of dyskinesia and underlie the priming process that characterise dyskinesia and its persistence.
authors.affiliation: Neurodegenerative Diseases Research Centre, Institute of Pharmaceutical Sciences, School of Biomedical Sciences, King's College, London, UK.
authors.forename: M M
authors.initials: MM
authors.lastname: Iravani
authors.forename: A C
authors.initials: AC
authors.lastname: McCreary
authors.forename: P
authors.initials: P
authors.lastname: Jenner
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa