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Nucleus Accumbens m G lu R 5‐Associated Signaling Regulates Binge Alcohol Drinking Under Drinking‐in‐the‐Dark Procedures
Author(s) -
Cozzoli Debra K.,
Courson Justin,
Caruana Amanda L.,
Miller Bailey W.,
Greentree Daniel I.,
Thompson Andrew B.,
Wroten Melissa G.,
Zhang PingWu,
Xiao Bo,
Hu JiaHua,
Klugmann Matthias,
Metten Pamela,
Worley Paul F.,
Crabbe John C.,
Szumlinski Karen K.
Publication year - 2012
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2012.01776.x
Subject(s) - nucleus accumbens , chemistry , alcohol , binge drinking , medicine , glutamate receptor , metabotropic glutamate receptor 5 , endocrinology , metabotropic glutamate receptor , receptor , pharmacology , biology , biochemistry , alcohol consumption
Background Alcohol increases the expression of Group 1 metabotropic glutamate receptors ( mG lu R s) and their associated scaffolding protein Homer2 and stimulates phosphatidylinositol 3‐kinase ( PI 3 K ) within the nucleus accumbens ( NAC ). Moreover, functional studies suggest that NAC Group 1 mG lu R / H omer2/ PI 3 K 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 m G lu R ‐associated proteins in C 57 BL /6 J ( B 6) mice. Follow‐up behavioral studies examined the importance of Group 1 m G lu R / H omer2/ PI 3 K signaling within the NAC shell for limited‐access alcohol drinking. Finally, immunoblotting examined whether the NAC expression of Group 1 m G lu R ‐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 m G lu R 5 and NR2B . Intra‐ NAC shell blockade of m G lu R 5, Homer2, or PI3K signaling, as well as transgenic disruption of the Homer binding site on m G lu R 5, decreased alcohol consumption in B 6 mice. Moreover, transgenic disruption of the Homer binding site on m G lu R 5 and Homer2 deletion both prevented the attenuating effect of m G lu R 5 and PI3K blockade upon intake. Finally, the basal NAC shell protein expression of m G lu R 1 and Homer2 was increased in offspring of HDID ‐1 animals. Conclusions Taken together, these data further implicate Group 1 m G lu R signaling through Homer2 within the NAC in excessive alcohol consumption.