[Correction added after online publication 10 May 2012: Andrew B. Thomspon corrected to Andrew B. Thompson.]
Nucleus Accumbens mGluR5-Associated Signaling Regulates Binge Alcohol Drinking Under Drinking-in-the-Dark Procedures
Article first published online: 20 MAR 2012
Copyright © 2012 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 36, Issue 9, pages 1623–1633, September 2012
How to Cite
Cozzoli, D. K., Courson, J., Caruana, A. L., Miller, B. W., Greentree, D. I., Thompson, A. B., Wroten, M. G., Zhang, P.-W., Xiao, B., Hu, J.-H., Klugmann, M., Metten, P., Worley, P. F., Crabbe, J. C. and Szumlinski, K. K. (2012), Nucleus Accumbens mGluR5-Associated Signaling Regulates Binge Alcohol Drinking Under Drinking-in-the-Dark Procedures. Alcoholism: Clinical and Experimental Research, 36: 1623–1633. doi: 10.1111/j.1530-0277.2012.01776.x
- Issue published online: 6 SEP 2012
- Article first published online: 20 MAR 2012
- Manuscript Accepted: 11 JAN 2012
- Manuscript Received: 26 MAY 2011
- National Institute on Alcohol Abuse and Alcoholism. Grant Number: AA016650
- KKS. Grant Numbers: AA13519, AA10760
- National Institute on Drug Abuse. Grant Numbers: DA00266, DA011742
- mGluR5 Receptors;
- PI3 Kinase;
- mGluR1 Receptors;
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.
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.
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.
Taken together, these data further implicate Group 1 mGluR signaling through Homer2 within the NAC in excessive alcohol consumption.