A potential role for adiponectin receptor 2 (AdipoR2) in the regulation of alcohol intake.
The anterior cingulate cortex (ACC) has been implicated in alcohol and drug addiction. We recently identified the small G protein K-ras as an alcohol-regulated gene in the ACC by gene expression analysis. We show here that the adiponectin receptor 2 (AdipoR2) was differentially regulated by alcohol in the ACC in a K-ras-dependent manner. Additionally, withdrawal-associated increased drinking was attenuated in AdipoR2 null mice. Intracellular recordings revealed that adiponectin increased the excitability of ACC neurons and that this effect was more pronounced during alcohol withdrawal, suggesting that AdipoR2 signaling may contribute to increased ACC activity. Altogether, the data implicate K-ras-regulated pathways involving AdipoR2 in the cellular and behavioral actions of alcohol that may contribute to overactivity of the ACC during withdrawal and excessive alcohol drinking.
Repunte-Canonigo
Vez
V
Molecular and Integrative Neuroscience Department, The Scripps Research Institute, La Jolla, CA 92037, USA.
Berton
Fulvia
F
Cottone
Pietro
P
Reifel-Miller
Anne
A
Roberts
Amanda J
AJ
Morales
Marisela
M
Francesconi
Walter
W
Sanna
Pietro Paolo
PP
D052242:Adiponectin / Q000378:metabolism*; D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000378:metabolism* / Q000633:toxicity; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020869:Gene Expression Profiling; D011905:Genes, ras; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D054419:Receptors, Adiponectin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D052242:Adiponectin; D054419:Receptors, Adiponectin; C475421:adiponectin receptor 2, mouse; C506573:adiponectin receptor 2, rat; D000431:Ethanol; D019204:GTP-Binding Proteins