RACK1 and brain-derived neurotrophic factor: A homeostatic pathway that regulates alcohol addiction

Nancy N.H. McGough, Dao Yao He, Marian L. Logrip, Jerome Jeanblanc, Khanhky Phamluong, Ken Luong, Viktor Kharazia, Patricia H. Janak, Dorit Ron

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)10542-10552
Number of pages11
JournalJournal of Neuroscience
Volume24
Issue number46
DOIs
StatePublished - Nov 17 2004
Externally publishedYes

Keywords

  • Addiction
  • Alcohol
  • BDNF
  • Drinking
  • RACK1
  • Self-administration

ASJC Scopus subject areas

  • General Neuroscience

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