Abstract:
:Compulsive behavior is a debilitating clinical feature of many forms of neuropsychiatric disease, including Tourette syndrome, obsessive-compulsive spectrum disorders, eating disorders, and autism. Although several studies link striatal dysfunction to compulsivity, the pathophysiology remains poorly understood. 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.
journal_name
Proc Natl Acad Sci U S Aauthors
Xu P,Grueter BA,Britt JK,McDaniel L,Huntington PJ,Hodge R,Tran S,Mason BL,Lee C,Vong L,Lowell BB,Malenka RC,Lutter M,Pieper AAdoi
10.1073/pnas.1308195110subject
Has Abstractpub_date
2013-06-25 00:00:00pages
10759-64issue
26eissn
0027-8424issn
1091-6490pii
1308195110journal_volume
110pub_type
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