期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：24
页码：11086-11091
DOI：10.1073/pnas.1000003107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Elevating serotonin (5-HT) levels with selective serotonin reuptake inhibitors (SSRIs) is the most widely used treatment for depression. However, current therapies are ineffective, have delayed benefit, or cause side effects in many patients. Here, we define a mechanism downstream of 5-HT1A receptors that mediates antidepressant-like behavior and is profoundly and selectively enhanced by genetic disruption of regulators of G protein signaling (RGS) activity at G{alpha}i2. Animals rendered insensitive to RGS protein regulation through a mutation in G{alpha}i2 (G184S) exhibited spontaneous antidepressant- and anxiolytic-like behaviors. Mice expressing RGS-insensitive G{alpha}i2 also exhibited increased cortical and hippocampal phosphorylation of glycogen synthase kinase-3{beta
关键词：5-HT1A receptors ; depression ; G protein ; regulator of G protein signaling proteins ; transgenic mouse
