{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:22:43Z","timestamp":1789748563667,"version":"4.0.1"},"reference-count":119,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T00:00:00Z","timestamp":1504742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Parkinson's disease (PD) is a neurodegenerative disorder associated with the progressive loss of nigrostriatal dopaminergic neurons. Levodopa is the most effective treatment for the motor symptoms of PD. However, chronic oral levodopa treatment can lead to various motor and nonmotor complications because of nonphysiological pulsatile dopaminergic stimulation in the brain. Examinations of autopsy cases with PD have revealed a decreased number of dendritic spines of striatal neurons. Animal models of PD have revealed altered density and morphology of dendritic spines of neurons in various brain regions after dopaminergic denervation or dopaminergic denervation plus levodopa treatment, indicating altered synaptic transmission. Recent studies using rodent models have reported dendritic spine head enlargement in the caudate\u2010putamen, nucleus accumbens, primary motor cortex, and prefrontal cortex in cases where chronic levodopa treatment following dopaminergic denervation induced dyskinesia\u2010like abnormal involuntary movement. Hypertrophy of spines results from insertion of alpha\u2010amino\u20102,3\u2010dihydro\u20105\u2010methyl\u20103\u2010oxo\u20104\u2010isoxazolepropanoic acid receptors into the postsynaptic membrane. Such spine enlargement indicates hypersensitivity of the synapse to excitatory inputs and is compatible with a lack of depotentiation, which is an electrophysiological hallmark of levodopa\u2010induced dyskinesia found in the corticostriatal synapses of dyskinetic animals and the motor cortex of dyskinetic PD patients. This synaptic plasticity may be one of the mechanisms underlying the priming of levodopa\u2010induced complications such as levodopa\u2010induced dyskinesia and dopamine dysregulation syndrome. Drugs that could potentially prevent spine enlargement, such as calcium channel blockers, N\u2010methyl\u2010D\u2010aspartate receptor antagonists, alpha\u2010amino\u20102,3\u2010dihydro\u20105\u2010methyl\u20103\u2010oxo\u20104\u2010isoxazolepropanoic acid receptor antagonists, and metabotropic glutamate receptor antagonists, are candidates for treatment of levodopa\u2010induced complications in PD. \u00a9 2017 The Authors.\n                    <jats:italic>Movement Disorders<\/jats:italic>\n                    published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.\n                  <\/jats:p>","DOI":"10.1002\/mds.27172","type":"journal-article","created":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T09:53:02Z","timestamp":1504777982000},"page":"877-888","source":"Crossref","is-referenced-by-count":51,"title":["Levodopa treatment and dendritic spine 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