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Here, we show that both constitutive and induced genetic deletion of the gene encoding the melanocortin 4 receptor (MC4R), as well as pharmacologic inhibition of MC4R signaling, normalize compulsive grooming and striatal electrophysiologic impairments in synapse-associated protein 90\/postsynaptic density protein 95-associated protein 3 (SAPAP3)-null mice, a model of human obsessive-compulsive disorder. Unexpectedly, genetic deletion of SAPAP3 restores normal weight and metabolic features of MC4R-null mice, a model of human obesity. Our findings offer insights into the pathophysiology and treatment of both compulsive behavior and eating disorders.<\/jats:p>","DOI":"10.1073\/pnas.1308195110","type":"journal-article","created":{"date-parts":[[2013,6,11]],"date-time":"2013-06-11T00:02:47Z","timestamp":1370908967000},"page":"10759-10764","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":41,"title":["Double deletion of melanocortin 4 receptors and SAPAP3 corrects compulsive behavior and obesity in mice"],"prefix":"10.1073","volume":"110","author":[{"given":"Pin","family":"Xu","sequence":"first","affiliation":[{"name":"Departments of aNeuroscience and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad A.","family":"Grueter","sequence":"additional","affiliation":[{"name":"Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremiah K.","family":"Britt","sequence":"additional","affiliation":[{"name":"Departments of cPsychiatry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Latisha","family":"McDaniel","sequence":"additional","affiliation":[{"name":"Departments of cPsychiatry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula J.","family":"Huntington","sequence":"additional","affiliation":[{"name":"Departments of aNeuroscience and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Hodge","sequence":"additional","affiliation":[{"name":"Departments of aNeuroscience and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Tran","sequence":"additional","affiliation":[{"name":"Departments of aNeuroscience and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany L.","family":"Mason","sequence":"additional","affiliation":[{"name":"Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Lee","sequence":"additional","affiliation":[{"name":"Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linh","family":"Vong","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradford B.","family":"Lowell","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Malenka","sequence":"additional","affiliation":[{"name":"Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lutter","sequence":"additional","affiliation":[{"name":"Departments of cPsychiatry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew A.","family":"Pieper","sequence":"additional","affiliation":[{"name":"Departments of cPsychiatry and"},{"name":"Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,6,10]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.comppsych.2010.05.007"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2008.83"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30897"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06104"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.08.035"},{"key":"e_1_3_3_6_2","first-page":"1","article-title":"Monogenic human obesity","volume":"36","author":"Farooqi IS","year":"2008","unstructured":"IS Farooqi, Monogenic human obesity. 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