title: Levodopa-induced dyskinesia is strongly associated with resonant cortical oscillations.
abstract: The standard pharmacological treatment for Parkinson's disease using the dopamine precursor levodopa is unfortunately limited by gradual development of disabling involuntary movements for which the underlying causes are poorly understood. Here we show that levodopa-induced dyskinesia in hemiparkinsonian rats is strongly associated with pronounced 80 Hz local field potential oscillations in the primary motor cortex following levodopa treatment. When this oscillation is interrupted by application of a dopamine antagonist onto the cortical surface the dyskinetic symptoms disappear. The finding that abnormal cortical oscillations are a key pathophysiological mechanism calls for a revision of the prevailing hypothesis that links levodopa-induced dyskinesia to an altered sensitivity to dopamine only in the striatum. Apart from having important implications for the treatment of Parkinson's disease, the discovered pathophysiological mechanism may also play a role in several other psychiatric and neurological conditions involving cortical dysfunction.
authors.affiliation: Neuronano Research Center, Department of Experimental Medical Science, Lund University, 22184 Lund, Sweden. Per.Petersson@med.lu.se
authors.forename: Pär
authors.initials: P
authors.lastname: Halje
authors.forename: Martin
authors.initials: M
authors.lastname: Tamtè
authors.forename: Ulrike
authors.initials: U
authors.lastname: Richter
authors.forename: Mohsin
authors.initials: M
authors.lastname: Mohammed
authors.forename: M Angela
authors.initials: MA
authors.lastname: Cenci
authors.forename: Per
authors.initials: P
authors.lastname: Petersson
mesh_terms: D000465:Algorithms; D000818:Animals; D000978:Antiparkinson Agents / Q000633:toxicity*; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D007980:Levodopa / Q000633:toxicity*; D008839:Microelectrodes; D017072:Neostriatum / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000145:classification; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D007980:Levodopa; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase