{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:24:46Z","timestamp":1791181486020,"version":"4.1.0"},"reference-count":80,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2006,10,25]],"date-time":"2006-10-25T00:00:00Z","timestamp":1161734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS19576"],"award-info":[{"award-number":["NS19576"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001671","name":"Hereditary Disease Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001671","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:p>An expansion in the CAG repeat of the IT15 (huntingtin) gene underlies the development of Huntington's disease (HD), but the basis for the specific vulnerability of dopamine\u2010receptive striatal neurons remains unclear. To examine the potential role of the dopamine system in the emergence of pathological conditions in HD, we generated a double mutant mouse strain with both enhanced dopamine transmission and endogenous expression of a mutant huntingtin gene. This strain was generated by crossing the dopamine transporter knock\u2010out mouse, which exhibits a 5\u2010fold elevation in extracellular dopamine levels in the striatum and locomotor hyperactivity, to a knock\u2010in mouse model of HD containing 92 CAG repeats. These double mutant mice exhibited an increased stereotypic activity at 6 months of age, followed by a progressive decline of their locomotor hyperactivity. Expression of the mutated huntingtin did not alter dopamine or its metabolite levels in normal or dopamine transporter knock\u2010out mice. However, the mutant huntingtin protein aggregated much earlier and to a greater extent in the striatum and other dopaminergic brain regions in the hyperdopaminergic mouse model of HD. Furthermore, the formation of neuropil aggregates in the striatum and other regions of hyperdopaminergic HD mice was observed at 4 months of age, well before similar events occurred in normal HD mice (12 months). These findings indicate that dopamine contributes to the deleterious effects of mutated huntingtin on striatal function, and this is accompanied by enhanced formation of huntingtin aggregates.\u2014Cyr, M., Sotnikova, T.D., Gainetdinov, R. R., Caron, M. G. Dopamine enhances motor and neuropathological consequences of polyglutamine expanded huntingtin. FASEB J. 20, E1866\u2013E1877 (2006)<\/jats:p>","DOI":"10.1096\/fj.06-6533fje","type":"journal-article","created":{"date-parts":[[2006,10,25]],"date-time":"2006-10-25T20:45:27Z","timestamp":1161809127000},"page":"2541-2543","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Dopamine enhances motor and neuropathological consequences of polyglutamine expanded huntingtin"],"prefix":"10.1096","volume":"20","author":[{"given":"Michel","family":"Cyr","sequence":"first","affiliation":[{"name":"Neuroscience Research Group, University of Quebec at Trois\u2010Rivieres Trois\u2010Rivieres Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana D.","family":"Sotnikova","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Center for Models of Human Disease, IGSP Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul R.","family":"Gainetdinov","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Center for Models of Human Disease, IGSP Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc G.","family":"Caron","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Center for Models of Human Disease, IGSP Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Cyr","sequence":"additional","affiliation":[{"name":"Neuroscience Research Group, University of Quebec at Trois\u2010Rivieres Trois\u2010Rivieres Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana D.","family":"Sotnikova","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Center for Models of Human Disease, IGSP Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul R.","family":"Gainetdinov","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Center for Models of Human Disease, IGSP Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc G.","family":"Caron","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Center for Models of Human Disease, IGSP Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,10,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4471-1308-9"},{"key":"e_1_2_6_3_1","volume-title":"A Disorder of Families","author":"Folstein S. E.","year":"1989"},{"key":"e_1_2_6_4_1","volume-title":"Huntington's Disease","author":"Harper P. S.","year":"1991"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0893-387"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0893-393"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/122.12.2353"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308679101"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90346-1"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2931802"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-198511000-00003"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(87)90694-9"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01568-X"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1831768100"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(70)90367-3"},{"key":"e_1_2_6_17_1","article-title":"Attitudes of those at risk for Huntington's disease toward presymptomatic provocative testing","volume":"307","author":"McCormack M. K.","year":"1982","journal-title":"N. Engl. J. Med"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-200211000-00003"},{"key":"e_1_2_6_19_1","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1097\/01.wco.0000084229.82329.03","article-title":"Huntington's disease: prospects for neuroprotective therapy 10 years after the discovery of the causative genetic mutation","volume":"16","author":"Hersch S. M.","year":"2003","journal-title":"Curr. Opin. Neurol"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.wnf.0000136892.24629.96"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.6.1.7"},{"key":"e_1_2_6_22_1","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1212\/01.wnl.0000198586.85250.13","article-title":"Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial","volume":"66","author":"The Huntington's Disease Collaborative Research Group","year":"2006","journal-title":"Neurology"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.12.1243"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0502698102"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/379606a0"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.4029"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.4.503"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5400.397"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80419-5"},{"key":"e_1_2_6_30_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.0030271","article-title":"Dopamine\u2010independent locomotor actions of amphetamines in a novel acute mouse model of Parkinson disease","volume":"3","author":"Sotnikova T. D.","year":"2005","journal-title":"PLoS Biol"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(00)00194-7"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-07-02522.1999"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-21-08473.2001"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-18-08266.2002"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80513-9"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5334.1990"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.12.1887"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-201X.1971.tb10998.x"},{"key":"e_1_2_6_39_1","first-page":"1","article-title":"Anatomy of the dopaminergic neuron systems in the rat brain","volume":"19","author":"Lindvall O.","year":"1978","journal-title":"Adv. Biochem. Psychopharmacol"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19991115)58:4<515::AID-JNR5>3.0.CO;2-F"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/2510"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(01)00261-3"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10776"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg169"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg075"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.10.037"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2004.08.008"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503634102"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80405-5"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02998"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-13-04861.1998"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1999.00764.x"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00778-9"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.71.3.310"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/119.6.2085"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410400110"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6480"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.9.1259"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.01.029"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(02)00216-4"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.86.6.2667"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.1244"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10272"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409402102"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00876.x"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2002.02047.x"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2005.01.039"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.09.005"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00188-0"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200412071"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi165"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-23-09112.2001"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)00427-7"},{"key":"e_1_2_6_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410370309"},{"key":"e_1_2_6_75_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.15.5733"},{"key":"e_1_2_6_76_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410270403"},{"key":"e_1_2_6_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(89)90074-X"},{"key":"e_1_2_6_78_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.15.030192.001441"},{"key":"e_1_2_6_79_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1991.00530200036015"},{"key":"e_1_2_6_80_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870100213"},{"key":"e_1_2_6_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-006-0014-x"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.06-6533fje","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.06-6533fje","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.06-6533fje","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T16:00:16Z","timestamp":1761667216000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.06-6533fje"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,10,25]]},"references-count":80,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2006,12]]}},"alternative-id":["10.1096\/fj.06-6533fje"],"URL":"https:\/\/doi.org\/10.1096\/fj.06-6533fje","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,10,25]]},"assertion":[{"value":"2006-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-07-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-10-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}