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Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson\u2019s disease. <i>Nature<\/i>, <b>334<\/b>, 345\u2013348 (1988).","DOI":"10.1038\/334345a0"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Jankovic J. Parkinson\u2019s disease: clinical features and diagnosis. <i>J. Neurol. Neurosurg. Psychiatry<\/i>, <b>79<\/b>, 368\u2013376 (2008).","DOI":"10.1136\/jnnp.2007.131045"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Chaudhuri KR, Healy DG, Schapira AH. Non-motor symptoms of Parkinson\u2019s disease: diagnosis and management. <i>Lancet Neurol.<\/i>, <b>5<\/b>, 235\u2013245 (2006).","DOI":"10.1016\/S1474-4422(06)70373-8"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Miyawaki E, Lyons K, Pahwa R, Tr\u00f6ster AI, Hubble J, Smith D, Busenbark K, McGuire D, Michalek D, Koller WC. Motor complications of chronic levodopa therapy in Parkinson\u2019s disease. <i>Clin. 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Neuropharmacol.<\/i>, <b>20<\/b>, 55\u201366 (1997).","DOI":"10.1097\/00002826-199702000-00007"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Calne DB, Reid JL, Vakil SD, Rao S, Petrie A, Pallis CA, Gawler J, Thomas PK, Hilson A. Idiopathic Parkinsonism treated with an extracerebral decarboxylase inhibitor in combination with levodopa. <i>BMJ<\/i>, <b>3<\/b>, 729\u2013732 (1971).","DOI":"10.1136\/bmj.3.5777.729"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Marsden CD, Parkes JD, Rees JE. A year\u2019s comparison of treatment of patients with Parkinson\u2019s disease with levodopa combined with carbidopa <i>versus<\/i> treatment with levodopa alone. <i>Lancet<\/i>, <b>302<\/b>, 1459\u20131462 (1973).","DOI":"10.1016\/S0140-6736(73)92729-3"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Kuruma I, Bartholini G, Tissot R, Pletscher A. The metabolism of L-3-O-methyldopa, a precursor of dopa in man. <i>Clin. Pharmacol. Ther.<\/i>, <b>12<\/b>, 678\u2013682 (1971).","DOI":"10.1002\/cpt1971124678"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Gasser UE, Crevoisier C, Ouwerkerk M, Lankhaar G, Dingemanse J. Comparative single- and multiple-dose pharmacokinetics of levodopa and 3-O-methyldopa following a new dual-release and a conventional slow-release formulation of levodopa and benserazide in healthy subjects. <i>Eur. J. Pharm. Biopharm.<\/i>, <b>46<\/b>, 223\u2013228 (1998).","DOI":"10.1016\/S0939-6411(98)00022-8"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Gomes P, Soares-da-Silva P. Interaction between L-DOPA and 3-O-methyl-L-DOPA for transport in immortalised rat capillary cerebral endothelial cells. <i>Neuropharmacology<\/i>, <b>38<\/b>, 1371\u20131380 (1999).","DOI":"10.1016\/S0028-3908(99)00042-8"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Reches A, Fahn S. 3-O-methyldopa blocks dopa metabolism in rat corpus striatum. <i>Ann. 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Bull.<\/i>, <b>35<\/b>, 1244\u20131248 (2012).","DOI":"10.1248\/bpb.b110714"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Maharaj H, Sukhdev Maharaj D, Scheepers M, Mokokong R, Daya S. l-DOPA administration enhances 6-hydroxydopamine generation. <i>Brain Res.<\/i>, <b>1063<\/b>, 180\u2013186 (2005).","DOI":"10.1016\/j.brainres.2005.09.041"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Baruzzi A, Contin M, Albani F, Riva R. Simple and rapid micromethod for the determination of levodopa and 3-O-methyldopa in human plasma by high-performance liquid chromatography with coulometric detection. <i>J. Chromatogr., Biomed. Appl.<\/i>, <b>375<\/b>, 165\u2013169 (1986).","DOI":"10.1016\/S0378-4347(00)83705-6"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Imanaka A, Morinobu S, Toki S, Yamawaki S. Importance of early environment in the development of post-traumatic stress disorder-like behaviors. <i>Behav. 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D1 dopamine receptors in prefrontal cortex: involvement in working memory. <i>Science<\/i>, <b>251<\/b>, 947\u2013950 (1991).","DOI":"10.1126\/science.1825731"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Durstewitz D, Seamans JK. The computational role of dopamine D1 receptors in working memory. <i>Neural Netw.<\/i>, <b>15<\/b>, 561\u2013572 (2002).","DOI":"10.1016\/S0893-6080(02)00049-7"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) da Silva WC, K\u00f6hler CC, Radiske A, Cammarota M. D1\/D5 dopamine receptors modulate spatial memory formation. <i>Neurobiol. Learn. Mem.<\/i>, <b>97<\/b>, 271\u2013275 (2012).","DOI":"10.1016\/j.nlm.2012.01.005"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Tran AH, Uwano T, Kimura T, Hori E, Katsuki M, Nishijo H, Ono T. Dopamine D1 receptor modulates hippocampal representation plasticity to spatial novelty. <i>J. 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