Ethanol-induced activation of AKT and DARPP-32 in the mouse striatum mediated by opioid receptors.
The reinforcing properties of ethanol are in part attributed to interactions between opioid and dopaminergic signaling pathways, but intracellular mediators of such interactions are poorly understood. Here we report that an acute ethanol challenge induces a robust phosphorylation of two key signal transduction kinases, AKT and DARPP-32, in the striatum of mice. Ethanol-induced AKT phosphorylation was blocked by the opioid receptor antagonist naltrexone but unaffected by blockade of dopamine D2 receptors via sulpiride. In contrast, DARPP-32 phosphorylation was abolished by both antagonists. These data suggest that ethanol acts via two distinct but potentially synergistic striatal signaling cascades. One of these is D2-dependent, while the other is not. These findings illustrate that pharmacology of ethanol reward is likely more complex than that for other addictive drugs.
Björk
Karl
K
Laboratory of Clinical and Translational Studies, NIAAA, National Institutes of Health, Bethesda, MD 20892-1108, USA.
Terasmaa
Anton
A
Sun
Hui
H
Thorsell
Annika
A
Sommer
Wolfgang H
WH
Heilig
Markus
M
D000435:Alcoholic Intoxication / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D015153:Blotting, Western; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D018492:Dopamine Antagonists / Q000494:pharmacology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology
D018492:Dopamine Antagonists; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009292:Narcotic Antagonists; C497929:Ppp1r1b protein, mouse; D017448:Receptors, Dopamine D2; D011957:Receptors, Opioid; D000431:Ethanol; D009271:Naltrexone; D013469:Sulpiride; D051057:Proto-Oncogene Proteins c-akt
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