Region-specific induction of FosB/ΔFosB by voluntary alcohol intake: effects of naltrexone

Alcohol Clin Exp Res. 2010 Oct;34(10):1742-50. doi: 10.1111/j.1530-0277.2010.01261.x. Epub 2010 Jul 9.


Background: ΔFosB is the best characterized transcription factor induced by chronic stimulation. Although previous studies have demonstrated that chronic passive ethanol exposure alters ΔFosB immunoreactivity (IR), the effect of chronic voluntary ethanol consumption on ΔFosB remains unknown. Furthermore, although previous studies have demonstrated that the opioid antagonist naltrexone reduces alcohol consumption in clinical and preclinical settings, the effect of naltrexone on FosB/ΔFosB has not been explored. Here, we examined the effects of chronic voluntary ethanol intake and naltrexone on FosB/ΔFosB IR in striatal region and prefrontal cortex, and the effect of naltrexone on voluntary ethanol intake.

Methods: We utilized immunohistochemistry to define the changes in FosB/ΔFosB IR induced by chronic voluntary ethanol intake under a two-bottle intermittent access of 20% ethanol model and by systematic administration (intraperitoneal injection) of naltrexone in Sprague-Dawley rats.

Results: Chronic (15 drinking sessions in 35 days) voluntary ethanol intake robustly induces FosB/ΔFosB IR in nucleus accumbens core, dorsolateral striatum, and orbitofrontal cortex, but not in nucleus accumbens shell, dorsomedial striatum, and medial prefrontal cortex. Systemic administration of naltrexone for 6 days significantly reduced voluntary ethanol consumption and FosB/ΔFosB IR induced by chronic voluntary ethanol intake.

Conclusion: Our results suggest that chronic voluntary ethanol intake induces FosB/ΔFosB IR in a subregion-specific manner which involves the activation of endogenous opioid system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcohol Drinking / adverse effects*
  • Alcohol Drinking / metabolism*
  • Animals
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism*
  • Drug Interactions
  • Naltrexone / pharmacology*
  • Narcotic Antagonists / pharmacology
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism*
  • Proto-Oncogene Proteins c-fos / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation / drug effects


  • Fosb protein, rat
  • Narcotic Antagonists
  • Proto-Oncogene Proteins c-fos
  • Naltrexone