RACK1 and brain-derived neurotrophic factor: a homeostatic pathway that regulates alcohol addiction.
Alcoholism is a devastating disease that manifests as uncontrolled drinking. Consumption of alcohol is regulated by neurochemical systems within specific neural circuits, but endogenous systems that may counteract and thus suppress the behavioral effects of ethanol intake are unknown. Here we demonstrate that BDNF plays a role in reducing the behavioral effects of ethanol, including consumption, in rodents. We found that decreasing the levels of BDNF leads to increased behavioral responses to ethanol, whereas increases in the levels of BDNF, mediated by the scaffolding protein RACK1, attenuate these behaviors. Interestingly, we found that acute exposure of neurons to ethanol leads to increased levels of BDNF mRNA via RACK1. Importantly, acute systemic administration of ethanol and voluntary ethanol consumption lead to increased levels of BDNF expression in the dorsal striatum. Taken together, these findings suggest that RACK1 and BDNF are part of a regulatory pathway that opposes adaptations that lead to the development of alcohol addiction.
McGough
Nancy N H
NN
Ernest Gallo Research Center, University of California, San Francisco, Emeryville, California 94608, USA.
He
Dao-Yao
DY
Logrip
Marian L
ML
Jeanblanc
Jerome
J
Phamluong
Khanhky
K
Luong
Ken
K
Kharazia
Viktor
V
Janak
Patricia H
PH
Ron
Dorit
D
D000428:Alcohol Drinking / Q000378:metabolism / Q000523:psychology*; D000437:Alcoholism / Q000378:metabolism / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000502:physiology*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D015696:Gene Products, tat / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012646:Self Administration
D019208:Brain-Derived Neurotrophic Factor; D015696:Gene Products, tat; D012333:RNA, Messenger; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D000431:Ethanol