Double deletion of melanocortin 4 receptors and SAPAP3 corrects compulsive behavior and obesity in mice.

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.

authors

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 AA

doi

10.1073/pnas.1308195110

subject

Has Abstract

pub_date

2013-06-25 00:00:00

pages

10759-64

issue

26

eissn

0027-8424

issn

1091-6490

pii

1308195110

journal_volume

110

pub_type

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