{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:09:58Z","timestamp":1789416598395,"version":"build-2803163510"},"reference-count":99,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T00:00:00Z","timestamp":1591660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T00:00:00Z","timestamp":1591660800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T00:00:00Z","timestamp":1591660800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"MRC","doi-asserted-by":"publisher","award":["MR\/S022465\/1"],"award-info":[{"award-number":["MR\/S022465\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"RSC Grant Project","award":["RG140118"],"award-info":[{"award-number":["RG140118"]}]},{"DOI":"10.13039\/501100000268","name":"BBSRC","doi-asserted-by":"publisher","award":["BB\/N504282\/3"],"award-info":[{"award-number":["BB\/N504282\/3"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Economia y Competitividad","doi-asserted-by":"publisher","award":["RTI2018-094374-B-I00"],"award-info":[{"award-number":["RTI2018-094374-B-I00"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 la Marat\u00f3 de TV3","doi-asserted-by":"publisher","award":["20140610"],"award-info":[{"award-number":["20140610"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007353","name":"Jerome Lejeune Foundation","doi-asserted-by":"publisher","award":["FJL-01\/01\/2013"],"award-info":[{"award-number":["FJL-01\/01\/2013"]}],"id":[{"id":"10.13039\/100007353","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Economia y Competitividad","doi-asserted-by":"publisher","award":["SAF2017-88076-R"],"award-info":[{"award-number":["SAF2017-88076-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Economia y Competitividad","doi-asserted-by":"publisher","award":["RTI2018-095311-B-I00"],"award-info":[{"award-number":["RTI2018-095311-B-I00"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["Supported by the intramural funds of the National Institute on Drug Abuse"],"award-info":[{"award-number":["Supported by the intramural funds of the National Institute on Drug Abuse"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Early Huntington\u2019s disease (HD) include over-activation of dopamine D1 receptors (D1R), producing an imbalance in dopaminergic neurotransmission and cell death. To reduce D1R over-activation, we present a strategy based on targeting complexes of D1R and histamine H3 receptors (H3R). Using an HD mouse striatal cell model and HD mouse organotypic brain slices we found that D1R-induced cell death signaling and neuronal degeneration, are mitigated by an H3R antagonist. We demonstrate that the D1R-H3R heteromer is expressed in HD mice at early but not late stages of HD, correlating with HD progression. In accordance, we found this target expressed in human control subjects and low-grade HD patients. Finally, treatment of HD mice with an H3R antagonist prevented cognitive and motor learning deficits and the loss of heteromer expression. Taken together, our results indicate that D1R - H3R heteromers play a pivotal role in dopamine signaling and represent novel targets for treating HD.<\/jats:p>","DOI":"10.7554\/elife.51093","type":"journal-article","created":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T20:00:20Z","timestamp":1591646420000},"source":"Crossref","is-referenced-by-count":35,"title":["Modulation of dopamine D1 receptors via histamine H3 receptors is a novel therapeutic target for Huntington's disease"],"prefix":"10.7554","volume":"9","author":[{"given":"David","family":"Moreno-Delgado","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9955-3558","authenticated-orcid":true,"given":"Mar","family":"Puigdell\u00edvol","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain"},{"name":"Department of Biomedical Science, Faculty of Medicine, University of Barcelona, Institut of Neuroscience, Barcelona, Spain"},{"name":"Institut d\u00b4Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain"},{"name":"School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefan\u00eda","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Rodr\u00edguez-Ruiz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6450-1267","authenticated-orcid":true,"given":"Joaqu\u00edn","family":"Botta","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, Barcelona, Spain"},{"name":"School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Gasperini","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Chiarlone","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain"},{"name":"Department of Biochemistry and Molecular Biology I, School of Biology, Instituto Universitario de Investigaci\u00f3n Neuroqu\u00edmica, and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria, Complutense University of Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley A","family":"Howell","sequence":"additional","affiliation":[{"name":"School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Scarselli","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicent","family":"Casad\u00f3","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergi","family":"Ferr\u00e9","sequence":"additional","affiliation":[{"name":"National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Guzm\u00e1n","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain"},{"name":"Department of Biochemistry and Molecular Biology I, School of Biology, Instituto Universitario de Investigaci\u00f3n Neuroqu\u00edmica, and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria, Complutense University of Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Llu\u00eds","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8684-2721","authenticated-orcid":true,"given":"Jordi","family":"Alberch","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain"},{"name":"Department of Biomedical Science, Faculty of Medicine, University of Barcelona, Institut of Neuroscience, Barcelona, Spain"},{"name":"Institut d\u00b4Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4992-7440","authenticated-orcid":true,"given":"Enric I","family":"Canela","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9479-8185","authenticated-orcid":true,"given":"Silvia","family":"Gin\u00e9s","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain"},{"name":"Department of Biomedical Science, Faculty of Medicine, University of Barcelona, Institut of Neuroscience, Barcelona, Spain"},{"name":"Institut d\u00b4Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2225-5181","authenticated-orcid":true,"given":"Peter J","family":"McCormick","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain"},{"name":"School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, United Kingdom"},{"name":"William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2020,6,9]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1523\/JNEUROSCI.3539-10.2011","article-title":"Differential electrophysiological changes in striatal output neurons in Huntington's disease","volume":"31","author":"Andr\u00e9","year":"2011","journal-title":"Journal of Neuroscience"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2011.00046","article-title":"Altered balance of activity in the striatal direct and indirect pathways in mouse models of Huntington's Disease","volume":"5","author":"Andr\u00e9","year":"2011","journal-title":"Frontiers in Systems Neuroscience"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.expneurol.2011.12.013","article-title":"Protein aggregates in Huntington's disease","volume":"238","author":"Arrasate","year":"2012","journal-title":"Experimental Neurology"},{"key":"bib4","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004302","article-title":"Heteromeric MT1\/MT2 melatonin receptors modulate photoreceptor function","volume":"6","author":"Baba","year":"2013","journal-title":"Science Signaling"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1124\/pr.110.002642","article-title":"The physiology, signaling, and pharmacology of dopamine receptors","volume":"63","author":"Beaulieu","year":"2011","journal-title":"Pharmacological Reviews"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"E3609","DOI":"10.1073\/pnas.1507704112","article-title":"Allosteric interactions between agonists and antagonists within the Adenosine A2A receptor-dopamine D2 receptor heterotetramer","volume":"112","author":"Bonaventura","year":"2015","journal-title":"PNAS"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"4411","DOI":"10.1172\/JCI74809","article-title":"Neurotrophin receptor p75(NTR) mediates Huntington's disease-associated synaptic and memory dysfunction","volume":"124","author":"Brito","year":"2014","journal-title":"Journal of Clinical Investigation"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1038\/mp.2014.73","article-title":"D1R\/GluN1 complexes in the striatum integrate dopamine and glutamate signalling to control synaptic plasticity and cocaine-induced responses","volume":"19","author":"Cahill","year":"2014","journal-title":"Molecular Psychiatry"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1677\/JME-10-0014","article-title":"Imaging of persistent cAMP signaling by internalized G protein-coupled receptors","volume":"45","author":"Calebiro","year":"2010","journal-title":"Journal of Molecular Endocrinology"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.tips.2010.02.002","article-title":"Signaling by internalized G-protein-coupled receptors","volume":"31","author":"Calebiro","year":"2010","journal-title":"Trends in Pharmacological Sciences"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1111\/j.1460-9568.2008.06038.x","article-title":"Differential electrophysiological properties of dopamine D1 and D2 receptor-containing striatal medium-sized spiny neurons","volume":"27","author":"Cepeda","year":"2008","journal-title":"The European Journal of Neuroscience"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000017294","article-title":"Dopamine and N-methyl-D-aspartate receptor interactions in the neostriatum","volume":"20","author":"Cepeda","year":"1998","journal-title":"Developmental Neuroscience"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.bbr.2013.07.016","article-title":"The prototypical histamine H3 receptor inverse agonist thioperamide improves multiple aspects of memory processing in an inhibitory avoidance task","volume":"253","author":"Charlier","year":"2013","journal-title":"Behavioural Brain Research"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"2448","DOI":"10.1152\/jn.00317.2006","article-title":"Dopamine D1\/5 receptor-mediated long-term potentiation of intrinsic excitability in rat prefrontal cortical neurons: ca2+-dependent intracellular signaling","volume":"97","author":"Chen","year":"2007","journal-title":"Journal of Neurophysiology"},{"key":"bib15","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2013.00114","article-title":"Dopamine imbalance in Huntington's disease: a mechanism for the lack of behavioral flexibility","volume":"7","author":"Chen","year":"2013","journal-title":"Frontiers in Neuroscience"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/nature12354","article-title":"Ultrasensitive fluorescent proteins for imaging neuronal activity","volume":"499","author":"Chen","year":"2013","journal-title":"Nature"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.nbd.2013.11.013","article-title":"Chronic blockade of extrasynaptic NMDA receptors ameliorates synaptic dysfunction and pro-death signaling in Huntington disease transgenic mice","volume":"62","author":"Dau","year":"2014","journal-title":"Neurobiology of Disease"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1016\/S1474-4422(11)70233-2","article-title":"Pridopidine for the treatment of motor function in patients with Huntington's disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial","volume":"10","author":"de Yebenes","year":"2011","journal-title":"The Lancet Neurology"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"15340","DOI":"10.1523\/JNEUROSCI.3144-11.2011","article-title":"Differential modulation of excitatory and inhibitory striatal synaptic transmission by histamine","volume":"31","author":"Ellender","year":"2011","journal-title":"Journal of Neuroscience"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1016\/j.nbd.2011.12.019","article-title":"P38 MAPK is involved in enhanced NMDA receptor-dependent excitotoxicity in YAC transgenic mouse model of Huntington disease","volume":"45","author":"Fan","year":"2012","journal-title":"Neurobiology of Disease"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.neuropharm.2008.05.008","article-title":"Interactions between histamine H3 and dopamine D2 receptors and the implications for striatal function","volume":"55","author":"Ferrada","year":"2008","journal-title":"Neuropharmacology"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1111\/j.1476-5381.2009.00152.x","article-title":"Marked changes in signal transduction upon heteromerization of dopamine D1 and histamine H3 receptors","volume":"157","author":"Ferrada","year":"2009","journal-title":"British Journal of Pharmacology"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"3877","DOI":"10.1523\/JNEUROSCI.11-12-03877.1991","article-title":"Proliferative and degenerative changes in striatal spiny neurons in Huntington's disease: a combined study using the section-Golgi method and calbindin D28k immunocytochemistry","volume":"11","author":"Ferrante","year":"1991","journal-title":"The Journal of Neuroscience"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"3010","DOI":"10.1152\/jn.00361.2002","article-title":"Dopamine enhancement of NMDA currents in dissociated medium-sized striatal neurons: role of D1 receptors and DARPP-32","volume":"88","author":"Flores-Hern\u00e1ndez","year":"2002","journal-title":"Journal of Neurophysiology"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1097\/WNF.0b013e3180ca77ea","article-title":"A study of chorea after tetrabenazine withdrawal in patients with Huntington disease","volume":"31","author":"Frank","year":"2008","journal-title":"Clinical Neuropharmacology"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1016\/j.cell.2011.09.055","article-title":"Decoding the signaling of a GPCR heteromeric complex reveals a unifying mechanism of action of antipsychotic drugs","volume":"147","author":"Fribourg","year":"2011","journal-title":"Cell"},{"key":"bib27","first-page":"199","article-title":"RP 67580, a potent and selective substance P non-peptide antagonist]","volume":"314","author":"Garret","year":"1992","journal-title":"Comptes Rendus De l'Academie Des Sciences. Serie III, Sciences De La Vie"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/S0091-3057(96)00295-X","article-title":"Different effects of dopamine antagonists on spontaneous and NMDA-induced motor activity in mice","volume":"56","author":"Gim\u00e9nez-Llort","year":"1997","journal-title":"Pharmacology Biochemistry and Behavior"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"21537","DOI":"10.1074\/jbc.M109.084202","article-title":"Impaired TrkB-mediated ERK1\/2 activation in Huntington disease knock-in striatal cells involves reduced p52\/p46 shc expression","volume":"285","author":"Gin\u00e9s","year":"2010","journal-title":"Journal of Biological Chemistry"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1093\/hmg\/ddr552","article-title":"Long-term memory deficits in Huntington's disease are associated with reduced CBP histone acetylase activity","volume":"21","author":"Giralt","year":"2012","journal-title":"Human Molecular Genetics"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1038\/mp.2011.93","article-title":"Dopamine D4 receptor, but not the ADHD-associated D4.7 variant, forms functional heteromers with the dopamine D2S receptor in the brain","volume":"17","author":"Gonz\u00e1lez","year":"2012","journal-title":"Molecular Psychiatry"},{"key":"bib32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001347","article-title":"Circadian-related heteromerization of adrenergic and dopamine D\u2084 receptors modulates melatonin synthesis and release in the pineal gland","volume":"10","author":"Gonz\u00e1lez","year":"2012","journal-title":"PLOS Biology"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.neuropharm.2013.03.005","article-title":"Homodimerization of Adenosine A\u2081 receptors in brain cortex explains the biphasic effects of caffeine","volume":"71","author":"Gracia","year":"2013","journal-title":"Neuropharmacology"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1006\/exnr.2000.7626","article-title":"Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production","volume":"169","author":"Guidetti","year":"2001","journal-title":"Experimental Neurology"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1124\/mol.114.093096","article-title":"Functional selectivity of allosteric interactions within G protein-coupled receptor oligomers: the dopamine D1-D3 receptor Receptor Heterotetramer","volume":"86","author":"Guitart","year":"2014","journal-title":"Molecular Pharmacology"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1152\/physrev.00043.2007","article-title":"Histamine in the nervous system","volume":"88","author":"Haas","year":"2008","journal-title":"Physiological Reviews"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1002\/cne.10837","article-title":"Estrogen increases the number of spinophilin-immunoreactive spines in the Hippocampus of young and aged female rhesus monkeys","volume":"465","author":"Hao","year":"2003","journal-title":"The Journal of Comparative Neurology"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"4806","DOI":"10.1096\/fj.14-254037","article-title":"A peptide targeting an interaction interface disrupts the dopamine D1-D2 receptor heteromer to block signaling and function in vitro and in vivo: effective selective antagonism","volume":"28","author":"Hasbi","year":"2014","journal-title":"The FASEB Journal"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"26","DOI":"10.4161\/pri.1.1.4056","article-title":"Aggregation of expanded huntingtin in the brains of patients with Huntington disease","volume":"1","author":"Hoffner","year":"2007","journal-title":"Prion"},{"key":"bib40","doi-asserted-by":"publisher","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":"Huntington Study Group","year":"2006","journal-title":"Neurology"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S0166-2236(00)01568-X","article-title":"Neuronal cell death in Huntington's disease: a potential role for dopamine","volume":"23","author":"Jakel","year":"2000","journal-title":"Trends in Neurosciences"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"S39","DOI":"10.1291\/hypres.18.SupplementI_S39","article-title":"Dopamine D1 receptor regulation of phospholipase C","volume":"18 Suppl 1","author":"Jose","year":"1995","journal-title":"Hypertension Research"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.neuron.2011.10.038","article-title":"Apo-ghrelin receptor forms heteromers with DRD2 in hypothalamic neurons and is essential for anorexigenic effects of DRD2 agonism","volume":"73","author":"Kern","year":"2012","journal-title":"Neuron"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.bbr.2004.11.008","article-title":"Effects of histamine H3 receptor antagonists in two models of spatial learning","volume":"159","author":"Komater","year":"2005","journal-title":"Behavioural Brain Research"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1124\/jpet.115.230771","article-title":"Histamine H3 receptor regulates sensorimotor gating and dopaminergic signaling in the striatum","volume":"357","author":"Kononoff Vanhanen","year":"2016","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.neuron.2011.05.036","article-title":"Endocytosis promotes rapid dopaminergic signaling","volume":"71","author":"Kotowski","year":"2011","journal-title":"Neuron"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1038\/nature05506","article-title":"Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson's disease models","volume":"445","author":"Kreitzer","year":"2007","journal-title":"Nature"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1093\/brain\/123.7.1349","article-title":"Visual object and visuospatial cognition in Huntington's disease: implications for information processing in corticostriatal circuits","volume":"123 ( Pt 7","author":"Lawrence","year":"2000","journal-title":"Brain"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"2632","DOI":"10.1096\/fj.13-246868","article-title":"Transmembrane peptides as unique tools to demonstrate the in vivo action of a cross\u2010class GPCR heterocomplex","volume":"28","author":"Lee","year":"2014","journal-title":"FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1007\/s00415-004-0461-9","article-title":"Cognitive changes in patients with Huntington's disease (HD) and asymptomatic carriers of the HD mutation--a longitudinal follow-up study","volume":"251","author":"Lemiere","year":"2004","journal-title":"Journal of Neurology"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s002210000397","article-title":"Segregation of working memory functions within the dorsolateral prefrontal cortex","volume":"133","author":"Levy","year":"2000","journal-title":"Experimental Brain Research"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1093\/hmg\/ddl125","article-title":"Genetic background modifies nuclear mutant huntingtin accumulation and HD CAG repeat instability in Huntington's disease knock-in mice","volume":"15","author":"Lloret","year":"2006","journal-title":"Human Molecular Genetics"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/nature12086","article-title":"Cell biology: receptor signals come in waves","volume":"495","author":"Lohse","year":"2013","journal-title":"Nature"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"601","DOI":"10.2174\/187152710793361531","article-title":"Regulation of corticostriatal synaptic plasticity by G protein-coupled receptors","volume":"9","author":"L\u00f3pez de Maturana","year":"2010","journal-title":"CNS & Neurological Disorders Drug Targets"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"4424","DOI":"10.1523\/JNEUROSCI.5113-06.2007","article-title":"Brain-derived neurotrophic factor restores synaptic plasticity in a knock-in mouse model of Huntington's disease","volume":"27","author":"Lynch","year":"2007","journal-title":"Journal of Neuroscience"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes","volume":"72","author":"Macdonald","year":"1993","journal-title":"Cell"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/S0092-8674(00)81369-0","article-title":"Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice","volume":"87","author":"Mangiarini","year":"1996","journal-title":"Cell"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"6186","DOI":"10.1073\/pnas.0931309100","article-title":"Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine","volume":"100","author":"Mattay","year":"2003","journal-title":"PNAS"},{"key":"bib59","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD006456","article-title":"Therapeutic interventions for symptomatic treatment in Huntington's disease","volume":"8","author":"Mestre","year":"2009","journal-title":"Cochrane. Database. Syst. Rev.CD"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"1690","DOI":"10.1093\/hmg\/ddl092","article-title":"Early development of aberrant synaptic plasticity in a mouse model of Huntington's disease","volume":"15","author":"Milnerwood","year":"2006","journal-title":"Human Molecular Genetics"},{"key":"bib61","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018336","article-title":"Altered dopamine and serotonin metabolism in motorically asymptomatic R6\/2 mice","volume":"6","author":"Mochel","year":"2011","journal-title":"PLOS ONE"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.neuropharm.2014.02.003","article-title":"Mechanism of the histamine H(3) receptor-mediated increase in exploratory locomotor activity and anxiety-like behaviours in mice","volume":"81","author":"Mohsen","year":"2014","journal-title":"Neuropharmacology"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"5846","DOI":"10.1074\/jbc.M110.161489","article-title":"Dopamine D1-histamine H3 receptor heteromers provide a selective link to MAPK signaling in GABAergic neurons of the direct striatal pathway","volume":"286","author":"Moreno","year":"2011","journal-title":"The Journal of Biological Chemistry"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"3545","DOI":"10.1523\/JNEUROSCI.4147-13.2014","article-title":"Cocaine disrupts histamine H3 receptor modulation of dopamine D1 receptor signaling: \u03c31-d1-h3 receptor complexes as key targets for reducing cocaine's effects","volume":"34","author":"Moreno","year":"2014","journal-title":"Journal of Neuroscience"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1111\/jnc.12739","article-title":"Iron dysregulation in Huntington's disease","volume":"130","author":"Muller","year":"2014","journal-title":"Journal of Neurochemistry"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"6639","DOI":"10.1523\/JNEUROSCI.4364-14.2015","article-title":"Orexin-corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine","volume":"35","author":"Navarro","year":"2015","journal-title":"Journal of Neuroscience"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/s002130100892","article-title":"Histamine H3-receptor blockade in the rat nucleus basalis magnocellularis improves place recognition memory","volume":"159","author":"Orsetti","year":"2002","journal-title":"Psychopharmacology"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1038\/nrn3526","article-title":"The histaminergic network in the brain: basic organization and role in disease","volume":"14","author":"Panula","year":"2013","journal-title":"Nature Reviews. Neuroscience"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"10090","DOI":"10.1523\/JNEUROSCI.3237-08.2008","article-title":"Dopaminergic and glutamatergic signaling crosstalk in Huntington's disease neurodegeneration: the role of p25\/cyclin-dependent kinase 5","volume":"28","author":"Paoletti","year":"2008","journal-title":"Journal of Neuroscience"},{"key":"bib70","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s00213-008-1171-2","article-title":"H3 receptor antagonists reverse delay-dependent deficits in novel object discrimination by enhancing retrieval","volume":"202","author":"Pascoli","year":"2009","journal-title":"Psychopharmacology"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/S0306-4522(02)00135-5","article-title":"A detailed mapping of the histamine H(3) receptor and its gene transcripts in rat brain","volume":"114","author":"Pillot","year":"2002","journal-title":"Neuroscience"},{"key":"bib72","doi-asserted-by":"publisher","first-page":"7265","DOI":"10.1093\/hmg\/ddv426","article-title":"A role for Kalirin-7 in corticostriatal synaptic dysfunction in Huntington's disease","volume":"24","author":"Puigdell\u00edvol","year":"2015","journal-title":"Human Molecular Genetics"},{"key":"bib73","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1111\/bpa.12432","article-title":"Cognitive dysfunction in Huntington's disease: mechanisms and therapeutic strategies beyond BDNF","volume":"26","author":"Puigdell\u00edvol","year":"2016","journal-title":"Brain Pathology"},{"key":"bib74","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1016\/j.euroneuro.2014.10.007","article-title":"Dysregulated intracellular signaling in the striatum in a pathophysiologically grounded model of tourette syndrome","volume":"24","author":"Rapanelli","year":"2014","journal-title":"European Neuropsychopharmacology"},{"key":"bib75","doi-asserted-by":"publisher","first-page":"21042","DOI":"10.1074\/jbc.M116.731406","article-title":"The histamine H3 receptor differentially modulates Mitogen-activated protein kinase (MAPK) and akt signaling in striatonigral and striatopallidal neurons","volume":"291","author":"Rapanelli","year":"2016","journal-title":"Journal of Biological Chemistry"},{"key":"bib76","doi-asserted-by":"publisher","first-page":"5733","DOI":"10.1073\/pnas.85.15.5733","article-title":"Differential loss of striatal projection neurons in Huntington disease","volume":"85","author":"Reiner","year":"1988","journal-title":"PNAS"},{"key":"bib77","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/S0079-6123(00)26030-5","article-title":"From arousal to cognition: the integrative position of the prefrontal cortex","volume":"126","author":"Robbins","year":"2000","journal-title":"Progress in Brain Research"},{"key":"bib78","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1212\/01.wnl.0000065888.88988.6e","article-title":"Evidence for more widespread cerebral pathology in early HD: an MRI-based morphometric analysis","volume":"60","author":"Rosas","year":"2003","journal-title":"Neurology"},{"key":"bib79","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/S1474-4422(10)70245-3","article-title":"Huntington's disease: from molecular pathogenesis to clinical treatment","volume":"10","author":"Ross","year":"2011","journal-title":"The Lancet Neurology"},{"key":"bib80","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/0304-3940(94)90279-8","article-title":"Marked increase in histamine H3 receptors in the striatum and substantia nigra after 6-hydroxydopamine-induced denervation of dopaminergic neurons: an autoradiographic study","volume":"178","author":"Ryu","year":"1994","journal-title":"Neuroscience Letters"},{"key":"bib81","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1097\/00001756-199401000-00022","article-title":"Heterogeneous distributions of histamine H3, dopamine D1 and D2 receptors in rat brain","volume":"5","author":"Ryu","year":"1994","journal-title":"NeuroReport"},{"key":"bib82","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.nlm.2004.03.003","article-title":"Late-associativity, synaptic tagging, and the role of dopamine during LTP and LTD","volume":"82","author":"Sajikumar","year":"2004","journal-title":"Neurobiology of Learning and Memory"},{"key":"bib83","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.neulet.2004.04.045","article-title":"Histamine H3 receptor activation inhibits dopamine D1 receptor-induced cAMP accumulation in rat striatal slices","volume":"364","author":"S\u00e1nchez-Lemus","year":"2004","journal-title":"Neuroscience Letters"},{"key":"bib84","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1038\/nn1869","article-title":"Rho mediates calcium-dependent activation of p38alpha and subsequent excitotoxic cell death","volume":"10","author":"Semenova","year":"2007","journal-title":"Nature Neuroscience"},{"key":"bib85","doi-asserted-by":"publisher","first-page":"4906","DOI":"10.1073\/pnas.0811228106","article-title":"Up-regulating BDNF with an ampakine rescues synaptic plasticity and memory in Huntington's disease knockin mice","volume":"106","author":"Simmons","year":"2009","journal-title":"PNAS"},{"key":"bib86","doi-asserted-by":"publisher","first-page":"2088","DOI":"10.1212\/WNL.43.10.2088","article-title":"Evidence for neuronal degeneration and dendritic plasticity in cortical pyramidal neurons of Huntington's disease: A quantitative Golgi study","volume":"43","author":"Sotrel","year":"1993","journal-title":"Neurology"},{"key":"bib87","doi-asserted-by":"publisher","first-page":"2799","DOI":"10.1111\/j.0953-816X.2004.03374.x","article-title":"Dendritic spine pathology and deficits in experience-dependent dendritic plasticity in R6\/1 Huntington's disease transgenic mice","volume":"19","author":"Spires","year":"2004","journal-title":"European Journal of Neuroscience"},{"key":"bib88","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1093\/cercor\/bhg121","article-title":"Estrogen replacement increases spinophilin-immunoreactive spine number in the prefrontal cortex of female rhesus monkeys","volume":"14","author":"Tang","year":"2004","journal-title":"Cerebral Cortex"},{"key":"bib89","doi-asserted-by":"publisher","first-page":"7899","DOI":"10.1523\/JNEUROSCI.1396-07.2007","article-title":"Dopaminergic signaling and striatal neurodegeneration in Huntington's disease","volume":"27","author":"Tang","year":"2007","journal-title":"The Journal of Neuroscience"},{"key":"bib90","doi-asserted-by":"publisher","first-page":"2313","DOI":"10.1523\/JNEUROSCI.4965-11.2013","article-title":"MAP kinase phosphatase 1 (MKP-1\/DUSP1) is neuroprotective in Huntington's disease via additive effects of JNK and p38 inhibition","volume":"33","author":"Taylor","year":"2013","journal-title":"Journal of Neuroscience"},{"key":"bib91","doi-asserted-by":"publisher","first-page":"2799","DOI":"10.1093\/hmg\/9.19.2799","article-title":"Dominant phenotypes produced by the HD mutation in STHdh(Q111) striatal cells","volume":"9","author":"Trettel","year":"2000","journal-title":"Human Molecular Genetics"},{"key":"bib92","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/nn1846","article-title":"Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory","volume":"10","author":"Vijayraghavan","year":"2007","journal-title":"Nature Neuroscience"},{"key":"bib93","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002194","article-title":"Cognitive impairment induced by Delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors","volume":"13","author":"Vi\u00f1als","year":"2015","journal-title":"PLOS Biology"},{"key":"bib94","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1097\/00005072-198511000-00003","article-title":"Neuropathological classification of Huntington's disease","volume":"44","author":"Vonsattel","year":"1985","journal-title":"Journal of Neuropathology and Experimental Neurology"},{"key":"bib95","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1097\/00005072-199805000-00001","article-title":"Huntington disease","volume":"57","author":"Vonsattel","year":"1998","journal-title":"Journal of Neuropathology and Experimental Neurology"},{"key":"bib96","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-5-18","article-title":"Tetrabenazine is neuroprotective in Huntington's disease mice","volume":"5","author":"Wang","year":"2010","journal-title":"Molecular Neurodegeneration"},{"key":"bib97","doi-asserted-by":"publisher","first-page":"3070","DOI":"10.1074\/jbc.M112.407726","article-title":"Dysregulation of mitochondrial calcium signaling and superoxide flashes cause mitochondrial genomic DNA damage in Huntington disease","volume":"288","author":"Wang","year":"2013","journal-title":"Journal of Biological Chemistry"},{"key":"bib98","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.344","article-title":"Possible use of a H3R antagonist for the management of nonmotor symptoms in the Q175 mouse model of Huntington's disease","volume":"5","author":"Whittaker","year":"2017","journal-title":"Pharmacology Research & Perspectives"},{"key":"bib99","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1002\/hipo.22340","article-title":"Antagonism of D1\/D5 receptors prevents long-term depression (LTD) and learning-facilitated LTD at the perforant path-dentate gyrus synapse in freely behaving rats","volume":"24","author":"Wiescholleck","year":"2014","journal-title":"Hippocampus"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/51093\/elife-51093-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/51093\/elife-51093-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/51093","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:57:06Z","timestamp":1697057826000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/51093"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,9]]},"references-count":99,"alternative-id":["10.7554\/eLife.51093"],"URL":"https:\/\/doi.org\/10.7554\/elife.51093","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/837658","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.51093.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.51093.sa1","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,9]]},"article-number":"e51093"}}