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Rotarod performance and locomotive activities were tested during the administration of the drug. The concentration of dopamine (<jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>) and its metabolites was quantified in the striatal tissues by high\u2010performance liquid chromatography (<jats:styled-content style=\"fixed-case\">HPLC<\/jats:styled-content>). Neuron survival in striatum and huntingtin protein aggregates were assessed with immunostaining. Expression levels of endoplasmic reticulum (<jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>) stress proteins were detected by immunoblotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Rotarod performance was significantly improved after treatment with low or middle dose of<jats:styled-content style=\"fixed-case\">NBI<\/jats:styled-content>\u2010641449 in<jats:styled-content style=\"fixed-case\">YAC<\/jats:styled-content>128 mice. Open field test showed that<jats:styled-content style=\"fixed-case\">NBI<\/jats:styled-content>\u2010641449 treatment could attenuate the increased horizontal activity (<jats:styled-content style=\"fixed-case\">HACTV<\/jats:styled-content>), total vertical movement, moving time, and moving distance in<jats:styled-content style=\"fixed-case\">YAC<\/jats:styled-content>128 mice. High dose of<jats:styled-content style=\"fixed-case\">NBI<\/jats:styled-content>\u2010641449 might cause sedative effects in<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">YAC<\/jats:styled-content>128 mice.<jats:styled-content style=\"fixed-case\">HPLC<\/jats:styled-content>showed that<jats:styled-content style=\"fixed-case\">NBI<\/jats:styled-content>\u2010641449 caused a dose\u2010dependent decrease of<jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content>, 3,4\u2010dihydroxyphenylacetic acid, and homovanillic acid levels in the striatum. NeuN and<jats:styled-content style=\"fixed-case\">DARPP<\/jats:styled-content>\u201032 immunostaining revealed that<jats:styled-content style=\"fixed-case\">NBI<\/jats:styled-content>\u2010641449 had no significant effect on the neuron survival in the striatum. However,<jats:styled-content style=\"fixed-case\">NBI<\/jats:styled-content>\u2010641449 treatment reduced the huntingtin protein aggregates in the cortex of<jats:styled-content style=\"fixed-case\">YAC<\/jats:styled-content>128 mice. In addition, the levels of<jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>stress proteins were increased in<jats:styled-content style=\"fixed-case\">YAC<\/jats:styled-content>128 mice, which can be suppressed by<jats:styled-content style=\"fixed-case\">NBI<\/jats:styled-content>\u2010641449.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that this new<jats:styled-content style=\"fixed-case\">VMAT<\/jats:styled-content>\u20102 inhibitor<jats:styled-content style=\"fixed-case\">NBI<\/jats:styled-content>\u2010641449 may have therapeutic potential for the treatment of<jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12425","type":"journal-article","created":{"date-parts":[[2015,6,30]],"date-time":"2015-06-30T11:09:07Z","timestamp":1435662547000},"page":"662-671","source":"Crossref","is-referenced-by-count":10,"title":["A New<scp>VMAT<\/scp>\u20102 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