{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:10:44Z","timestamp":1793725844703,"version":"4.6.1"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,3,25]],"date-time":"2002-03-25T00:00:00Z","timestamp":1017014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2002,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In both Huntington's disease (HD) patients and genetic mouse models of HD, there is a pre\u2010symptomatic loss of dopamine (DA) receptors, suggesting that dysfunctional dopaminergic neurotransmission may be involved in early HD presentation. However, the role of DA in HD symptoms is not fully understood. In this study, we examined the possibility that dysfunctional dopaminergic neurotransmission contributes to the progressive decline in motor function of a transgenic mouse model of HD (R6\/2 line). We found that R6\/2 mice display an age\u2010dependent abnormal behavioural response to (+)\u2010methamphetamine (METH) and a dose\u2010dependent increase in sensitivity to METH toxicity compared with wildtype (WT) mice. R6\/2 mice also showed an attenuated response to cocaine, indicating that DA release may be compromised. Striatal DA levels were reduced in R6\/2 mice by 9\u2003weeks of age. Replacement of DA by chronic treatment with laevodopa (<jats:sc>l<\/jats:sc>\u2010DOPA, administered as Sinemet) caused short\u2010term improvements in activity and rearing behaviour, and abolished abnormal spontaneous hindlimb grooming. However, long\u2010term treatment with <jats:sc>l<\/jats:sc>\u2010DOPA had deleterious effects on survival and rotarod performance of R6\/2 mice. These results suggest that dysfunctional DA neurotransmission contributes to phenotype development in R6\/2 mice and thus also may be important in symptom progression in HD.<\/jats:p>","DOI":"10.1046\/j.1471-4159.2002.00804.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T06:59:42Z","timestamp":1047452382000},"page":"46-59","source":"Crossref","is-referenced-by-count":97,"title":["The role of dopamine in motor symptoms in the R6\/2 transgenic mouse model of Huntington's disease"],"prefix":"10.1111","volume":"81","author":[{"given":"Miriam A.","family":"Hickey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin P.","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Jennifer","family":"Morton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,3,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/119.6.2085"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(98)00020-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/1467-9450.00238"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"4181","DOI":"10.1523\/JNEUROSCI.13-10-04181.1993","article-title":"Neurochemical and histologic characterisation of striatal excitotoxic lesions produced by the mitochondrial toxin 3\u2010nitropropionic acid","volume":"81","author":"Beal M. F.","year":"1993","journal-title":"J. Neurosci."},{"key":"e_1_2_7_6_1","first-page":"525","volume-title":"Brain Amines in Huntington's Chorea","author":"Bernheimer H.","year":"1973"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.120166397"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0301-0082(99)00005-2","article-title":"Replicating Huntington's disease phenotype in experimental animals","volume":"81","author":"Brouillet E.","year":"1999","journal-title":"Prog. Neurobiol."},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(00)00098-2"},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","first-page":"3248","DOI":"10.1523\/JNEUROSCI.19-08-03248.1999","article-title":"Characterization of progressive motor deficits in mice transgenic for the Huntington's disease mutation","volume":"81","author":"Carter R. J.","year":"1999","journal-title":"J. Neurosci."},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8257(200009)15:5<925::AID-MDS1025>3.0.CO;2-Z"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142301.ns0812s15"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6480"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1098\/rstb.1999.0449","article-title":"Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's disease","volume":"81","author":"Cha J.\u2010H. J.","year":"1999","journal-title":"Phil. Trans. R. Soc. Lond. (Biol.)."},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1978.00500250031006"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80513-9"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.14.5274"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1998.6926"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(99)00776-1"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00639-7"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/120.3.503"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0887-8994(95)00225-1"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(84)90028-5"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00691103"},{"key":"e_1_2_7_25_1","unstructured":"HarperP. S.Ed. (1996)Major Problems in Neurology 81:Huntington's Disease.2nd edn.W. B. Saunders Co. Ltd. London."},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-000-0007-0"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0752163.x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.3.649"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01568-X"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90292-5"},{"key":"e_1_2_7_31_1","doi-asserted-by":"crossref","first-page":"4405","DOI":"10.1523\/JNEUROSCI.20-12-04405.2000","article-title":"Dopamine\u2010deficient mice are hypersensitive to dopamine receptor agonists","volume":"81","author":"Kim D. S.","year":"2000","journal-title":"J. Neurosci."},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-5748(00)00022-8"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(90)90480-T"},{"key":"e_1_2_7_34_1","first-page":"1085","article-title":"Differential effects of amphetamine and dopamine uptake blockers (cocaine, nomifensine) on caudate and accumbens dialysate dopamine and 3\u2010methoxytyramine","volume":"81","author":"Kuczenski R.","year":"1992","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_35_1","doi-asserted-by":"crossref","first-page":"10428","DOI":"10.1523\/JNEUROSCI.19-23-10428.1999","article-title":"Selective discrimination learning impairments in mice expressing the human Huntington's disease mutation","volume":"81","author":"Lione L. A.","year":"1999","journal-title":"J. Neurosci."},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.39.10.958"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81369-0"},{"key":"e_1_2_7_38_1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1152\/physrev.1998.78.1.189","article-title":"Dopamine receptors: from structure to function","volume":"81","author":"Missale C.","year":"1998","journal-title":"Physiol. Rev."},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00059.x"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(98)00097-5"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0013-4694(72)90177-0"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01256491"},{"key":"e_1_2_7_43_1","doi-asserted-by":"crossref","first-page":"10116","DOI":"10.1523\/JNEUROSCI.18-23-10116.1998","article-title":"Dopamine modulates that susceptibility of striatal neurons to 3\u2010nitropropionic acid in the rat model of Huntington's disease","volume":"81","author":"Reynolds D. S.","year":"1998","journal-title":"J. Neurosci."},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.721773.x"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(89)80054-5"},{"key":"e_1_2_7_46_1","first-page":"S12","article-title":"Dopamine receptors and locomotor responses: molecular aspects","volume":"81","author":"Sealfon S. C.","year":"2000","journal-title":"Ann. Neurol."},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02191583"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.2000.19640617.x"},{"key":"e_1_2_7_49_1","first-page":"37","article-title":"Evidence of early onset of antidepressant effect in randomised controlled trials","volume":"81","author":"Stahl S. M.","year":"2001","journal-title":"J. Clin. Psychiatry."},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.21.12138"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00319-1"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.53.7.1605"},{"key":"e_1_2_7_53_1","first-page":"971","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes","volume":"81","author":"The Huntington's Disease Collaborative Research Group","year":"1993","journal-title":"Cell."},{"key":"e_1_2_7_54_1","first-page":"823","article-title":"Effects of bromocriptine in Huntington chorea case report","volume":"81","author":"Tsuneizumi T.","year":"1994","journal-title":"Prog. Neuropsychopharmacol. Biol. Psych."},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410400110"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90145-0"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1471-4159.2002.00804.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1046\/j.1471-4159.2002.00804.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T19:02:25Z","timestamp":1697569345000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1046\/j.1471-4159.2002.00804.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,3,25]]},"references-count":55,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2002,4]]}},"alternative-id":["10.1046\/j.1471-4159.2002.00804.x"],"URL":"https:\/\/doi.org\/10.1046\/j.1471-4159.2002.00804.x","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,3,25]]}}}