{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T13:17:19Z","timestamp":1772889439895,"version":"3.50.1"},"reference-count":79,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,8,22]],"date-time":"2017-08-22T00:00:00Z","timestamp":1503360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005725","name":"CHDI Foundation","doi-asserted-by":"publisher","award":["A\u20108746"],"award-info":[{"award-number":["A\u20108746"]}],"id":[{"id":"10.13039\/100005725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Huntington's disease (<jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>) is an autosomal dominant, neurodegenerative disorder characterized by motor as well as nonmotor symptoms for which there is currently no cure. The Q175 mouse model of <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> recapitulates many of the symptoms identified in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> patients including disruptions of the sleep\/wake cycle. In this study, we sought to determine if the daily administration of the histamine\u20103 receptor (H3R) antagonist\/inverse agonist 6\u2010[(3\u2010cyclobutyl\u20102,3,4,5\u2010tetrahydro\u20101H\u20103\u2010benzazepin\u20107\u2010yl)oxy]\u2010N\u2010methyl\u20103\u2010pyridinecarboxamide hydrochloride (<jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>189254) would improve nonmotor symptoms in the Q175 line. This class of drugs acts on autoreceptors found at histaminergic synapses and results in increased levels of histamine (<jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> is a neuromodulator whose levels vary with a daily rhythm with peak release during the active cycle and relatively lower levels during sleep. H3Rs are widely expressed in brain regions involved in cognitive processes and activation of these receptors promotes wakefulness. We administered <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>189254 nightly to homozygote and heterozygote Q175 mice for 4\u00a0weeks and confirmed that the plasma levels of the drug were elevated to a therapeutic range. We demonstrate that daily treatment with <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>189254 improved several behavioral measures in the Q175 mice including strengthening activity rhythms, cognitive performance and mood as measured by the tail suspension test. The treatment also reduced inappropriate activity during the normal sleep time. The drug treatment did not alter motor performance and coordination as measured by the challenging beam test. Our findings suggest that drugs targeting the H3R system may show benefits as cognitive enhancers in the management of <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/prp2.344","type":"journal-article","created":{"date-parts":[[2017,9,2]],"date-time":"2017-09-02T00:44:33Z","timestamp":1504313073000},"source":"Crossref","is-referenced-by-count":23,"title":["Possible use of a H3R antagonist for the management of nonmotor symptoms in the Q175 mouse model of Huntington's disease"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4293-5192","authenticated-orcid":false,"given":"Daniel S.","family":"Whittaker","sequence":"first","affiliation":[{"name":"Department of Psychiatry &amp; Biobehavioral Sciences University of California Los Angeles California 90095\u20101751"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huei\u2010Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry &amp; Biobehavioral Sciences University of California Los Angeles California 90095\u20101751"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawn H.","family":"Loh","sequence":"additional","affiliation":[{"name":"Department of Psychiatry &amp; Biobehavioral Sciences University of California Los Angeles California 90095\u20101751"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger","family":"Cachope","sequence":"additional","affiliation":[{"name":"CHDI Foundation 6080 Center Drive Suite 100 Los Angeles California 90045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1059-184X","authenticated-orcid":false,"given":"Christopher S.","family":"Colwell","sequence":"additional","affiliation":[{"name":"Department of Psychiatry &amp; Biobehavioral Sciences University of California Los Angeles California 90095\u20101751"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,8,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbrainres.2004.02.015"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/302832a0"},{"key":"e_1_2_9_4_1","volume-title":"Methods of behavior analysis in neuroscience","author":"Bailey KR","year":"2009"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152707779940790"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705964"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0278-5846(88)90014-0"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-009-9102-7"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.10.031"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(00)00039-3"},{"key":"e_1_2_9_11_1","first-page":"e3769","article-title":"The tail suspension test","volume":"59","author":"Can A","year":"2011","journal-title":"J Vis Exp"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401967"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90465-Y"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2005.03.009"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.2"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11920-014-0524-2"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0893-387"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)00635-4"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/0748730411431550"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3080-04.2004"},{"key":"e_1_2_9_21_1","first-page":"50303","article-title":"Assessment of sensorimotor function in mouse models of Parkinson's disease","volume":"76","author":"Fleming SM","year":"2013","journal-title":"J Vis Exp"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.078402"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.158444"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.61.1.239"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.266"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.04.033"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00205.x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26001"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1034"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.13.10.1237"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0050717"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.23.13316"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1159\/000125220"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9384(90)90125-N"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9384(91)90293-W"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(00)01504-2"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2006.08.016"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13030"},{"key":"e_1_2_9_39_1","first-page":"e4367","article-title":"The resident\u2010intruder paradigm: a standardized test for aggression, violence and social stress","volume":"77","author":"Koolhaas JM","year":"2013","journal-title":"J Vis Exp"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2010.12.011"},{"key":"e_1_2_9_41_1","first-page":"93","article-title":"Sleep and circadian dysfunction in neurodegenerative disorders: insights from a mouse model of Huntington's disease","volume":"51","author":"Kuljis D","year":"2012","journal-title":"Minerva Pneumol"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30992"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2015.03.009"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)91508-E"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.12.003"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.170134"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0069993"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1373\/49.10.1726"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06249.x"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)91240-H"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.120311"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049838"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1177\/074873098129000129"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04387.x"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9384(92)90157-W"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/35048583"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3842-04.2005"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00139.2006"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-17-07695.2002"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2004.10.003"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.10518"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00135-5"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(93)90191-H"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3570"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1838(92)90050-Q"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(03)01272-X"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.10.039"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0144694"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20373"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.02.003"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.1838"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4286-09.2009"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.053249"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2010.00465.x"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbscr.2016.12.002"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(84)90811-4"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308679101"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2013.09.090"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-05-01787.2001"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2004.05.001"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fprp2.344","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.344","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T10:47:56Z","timestamp":1696502876000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,22]]},"references-count":79,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1002\/prp2.344"],"URL":"https:\/\/doi.org\/10.1002\/prp2.344","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,22]]},"article-number":"e00344"}}