Nucleus Accumbens mGluR5-Associated Signaling Regulates Binge Alcohol Drinking Under Drinking-in-the-Dark Procedures

被引：92

作者：

Cozzoli, Debra K. ^{[1
]}

Courson, Justin ^{[1
]}

Caruana, Amanda L. ^{[1
]}

Miller, Bailey W. ^{[1
]}

Greentree, Daniel I. ^{[1
]}

Thompson, Andrew B. ^{[1
]}

Wroten, Melissa G. ^{[1
]}

Zhang, Ping-Wu ^{[2
]}

Xiao, Bo ^{[2
]}

Hu, Jia-Hua ^{[2
]}

Klugmann, Matthias ^{[3
]}

Metten, Pamela ^{[4
]}

Worley, Paul F. ^{[2
]}

Crabbe, John C. ^{[4
]}

Szumlinski, Karen K. ^{[1
]}

机构：

[1] Univ Calif Santa Barbara, Dept Psychol & Brain Sci, Neurosci Res Inst, Santa Barbara, CA 93106 USA

[2] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

[3] Univ New S Wales, Sch Med Sci, Translat Neurosci Facil, Sydney, NSW 2052, Australia

[4] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA

来源：

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH | 2012年 / 36卷 / 09期

关键词：

mGluR5; Receptors; PI3; Kinase; Homer; mGluR1; HDID-1; NR2B-CONTAINING NMDA RECEPTORS; POSTSYNAPTIC DENSITY PROTEINS; LONG-LASTING ADAPTATIONS; MALE C57BL/6J MICE; ETHANOL DRINKING; INDUCED NEUROPLASTICITY; DORSOMEDIAL STRIATUM; STRAIN DIFFERENCES; MAMMALIAN TARGET; P RATS;

D O I：

10.1111/j.1530-0277.2012.01776.x

中图分类号：

R194 [卫生标准、卫生检查、医药管理];

学科分类号：

摘要：

Background Alcohol increases the expression of Group 1 metabotropic glutamate receptors (mGluRs) and their associated scaffolding protein Homer2 and stimulates phosphatidylinositol 3-kinase (PI3K) within the nucleus accumbens (NAC). Moreover, functional studies suggest that NAC Group 1 mGluR/Homer2/PI3K signaling may be a potential target for pharmacotherapeutic intervention in alcoholism. Methods Immunoblotting was conducted to examine the effects of alcohol consumption under drinking-in-the-dark (DID) procedures on Group 1 mGluR-associated proteins in C57BL/6J (B6) mice. Follow-up behavioral studies examined the importance of Group 1 mGluR/Homer2/PI3K signaling within the NAC shell for limited-access alcohol drinking. Finally, immunoblotting examined whether the NAC expression of Group 1 mGluR-associated proteins is a genetic correlate of high alcohol drinking using a selectively bred high DID (HDID-1) mouse line. Results Limited-access alcohol drinking under DID procedures up-regulated NAC shell Homer2 levels, concomitant with increases in mGluR5 and NR2B. Intra-NAC shell blockade of mGluR5, Homer2, or PI3K signaling, as well as transgenic disruption of the Homer binding site on mGluR5, decreased alcohol consumption in B6 mice. Moreover, transgenic disruption of the Homer binding site on mGluR5 and Homer2 deletion both prevented the attenuating effect of mGluR5 and PI3K blockade upon intake. Finally, the basal NAC shell protein expression of mGluR1 and Homer2 was increased in offspring of HDID-1 animals. Conclusions Taken together, these data further implicate Group 1 mGluR signaling through Homer2 within the NAC in excessive alcohol consumption.

引用

页码：1623 / 1633

页数：11