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This nondopaminergic involvement impacts on the generation of symptoms, on the neurodegenerative process, but, most tellingly, in the generation of side effects of current treatments, in particular, levodopa\u2010induced dyskinesia (LID). Such mechanisms contribute not only to the expression of LID once it has been established but also to the mechanisms responsible for the development, or priming, of the dyskinetic state and the subsequent maintenance of the brain in that primed state. Within the basal ganglia, abnormalities in different nondopaminergic components of the circuitry have been defined in LID. In particular, a role for enhanced inhibition of basal ganglia outputs by the GABAergic direct pathway has been suggested as a basic mechanism generating LID. We speculate that the external globus pallidus and subthalamic nucleus may play distinct roles in different forms of dyskinesia, e.g., chorea\/dystonia; peak\/diphasic\/<jats:italic>off<\/jats:italic>. At the cellular level, an appreciation of abnormal signaling by, among others, glutamatergic (NMDA and AMPA receptors in particular), \u03b1<jats:sub>2<\/jats:sub> adrenergic, serotonergic (5HT), cannabinoid and opioid mechanisms in both priming and expression of LID has begun to emerge over the last decade. This is being consolidated, though in many cases questions remain regarding the specific sites of such abnormality within the circuitry. Very recently, at the molecular level, mechanisms controlling neurotransmitter release and impacting on the ability of neurons to maintain particular forms of firing patterning and synchronization, e.g., SV2A, have been identified. This increased understanding has already delivered and will continue to define novel approaches to treatment that target both pre\u2010 and postsynaptic signaling molecules throughout the basal ganglia circuitry. \u00a9 2005 Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.20612","type":"journal-article","created":{"date-parts":[[2005,7,8]],"date-time":"2005-07-08T18:54:47Z","timestamp":1120848887000},"page":"919-931","source":"Crossref","is-referenced-by-count":172,"title":["Nondopaminergic mechanisms in levodopa\u2010induced dyskinesia"],"prefix":"10.1002","volume":"20","author":[{"given":"Jonathan 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