{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:01:33Z","timestamp":1791270093909,"version":"4.1.0"},"reference-count":66,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2013,10,9]],"date-time":"2013-10-09T00:00:00Z","timestamp":1381276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>About a half a century has passed since dopamine was identified as a neurotransmitter, and it has been several decades since it was established that people with Parkinson's disease receive motor symptom relief from oral levodopa. Despite the evidence that levodopa can reduce motor symptoms, there has been a developing body of literature that dopaminergic therapy can improve cognitive functions in some patients but make them worse in others. Over the past two decades, several laboratories have shown that dopaminergic medications can impair the action of intact neural structures and impair the behaviors associated with these structures. In this review, we consider the evidence that has accumulated in the areas of reversal learning, motor sequence learning, and other cognitive tasks. The purported inverted\u2010U shaped relationship between dopamine levels and performance is complex and includes many contributory factors. The regional striatal topography of nigrostriatal denervation is a critical factor, as supported by multimodal neuroimaging studies. A patient's individual genotype will determine the relative baseline position on this inverted\u2010U curve. Dopaminergic pharmacotherapy and individual gene polymorphisms can affect the mesolimbic and prefrontal cortical dopaminergic functions in a comparable, inverted\u2010U dose\u2010response relationship. Depending on these factors, a patient can respond positively or negatively to levodopa when performing reversal learning and motor sequence learning tasks. These tasks may continue to be relevant as our society moves to increased technological demands of a digital world that requires newly learned motor sequences and adaptive behaviors to manage daily life activities. \u00a9 2013 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.25687","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T21:55:54Z","timestamp":1381528554000},"page":"1920-1929","source":"Crossref","is-referenced-by-count":165,"title":["Dopamine overdose hypothesis: Evidence and clinical implications"],"prefix":"10.1002","volume":"28","author":[{"given":"David E.","family":"Vaillancourt","sequence":"first","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida Gainesville Florida USA"},{"name":"Department of Neurology University of Florida Gainesville Florida USA"},{"name":"Department of Biomedical Engineering University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Schonfeld","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngbin","family":"Kwak","sequence":"additional","affiliation":[{"name":"Center for Cognitive Neuroscience Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaas I.","family":"Bohnen","sequence":"additional","affiliation":[{"name":"Neurology Service and Geriatric Research Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, University of Michigan Ann Arbor Michigan USA"},{"name":"Department of Neurology University of Michigan Ann Arbor Michigan USA"},{"name":"Department of Radiology University of Michigan Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Seidler","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Michigan Ann Arbor Michigan USA"},{"name":"Department of Psychology University of Michigan Ann Arbor Michigan USA"},{"name":"School of Kinesiology University of Michigan Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,9]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/1801200a0"},{"key":"e_1_2_5_3_1","volume-title":"Movement Disorders: Neurologic Principles and Practice","author":"Watts RL","year":"2004"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/11.12.1136"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00197.2009"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2005.03.024"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/111.2.299"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3932(99)00103-7"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70212-X"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22836"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(10)83014-6"},{"key":"e_1_2_5_12_1","first-page":"231","article-title":"Evidence for the existence of monoamine\u2010containing neurons in the central nervous system. 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