Ethanol-sensitive brain regions in rat and mouse: a cartographic review, using immediate early gene expression

Alcohol Clin Exp Res. 2009 Jun;33(6):945-69. doi: 10.1111/j.1530-0277.2009.00916.x. Epub 2009 Mar 19.


Background: Ethanol addiction has been conceptualized as a progression from occasional, impulsive use to compulsive behavior. Ethanol-dependence is a chronic pathology with repeated cycles of withdrawal, craving, and relapse. Specific molecular and cellular mechanisms underlie these transition stages.

Methods: This review aimed at elucidating whether there are also adaptations in the pattern of brain regions responding to ethanol. This paper reviews the evidence in rodents for activation of specific brain regions, assessed by induction of IEG expression, following acute and chronic ethanol exposure.

Results: The review sheds light on the specific patterns of response in regions of the brain to different types of ethanol exposure and shows that activation of specific brain regions may occur in particular phases of the development of ethanol addiction. Some brain regions respond consistently following acute or chronic treatments or withdrawal: the prefrontal cortex; nucleus accumbens; lateral septum; hippocampus; perioculomotor urocortin-containing cells population (pIIIu), also known as Edinger-Westphal nucleus; central nucleus of the amygdala; and the paraventricular nucleus of hypothalamus. The two last brain areas are particularly activated by relapse-inducing stressors. It is of interest that the amygdala, hippocampus, and prefrontal cortex, which belong to the reward system, are activated by cue-induced relapse to ethanol self-administration in rodents and humans, while activation of these regions is reversed with anti-craving compounds. Following chronic exposure, IEG induction desensitizes while withdrawal reactivates these regions.

Discussion: Some responding regions are implicated in reward related processes (VTA, extended amygdala, hypothalamus, hippocampus, prelimbic cortex, ventral part of lateral septum) and some others in aversive-related processes (area postrema, nucleus of solitary tract).

Conclusion: A better understanding of the neural circuits affected by ethanol and their adaptations during the development of ethanol addiction will provide new opportunities for developing appropriate therapies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alcoholism / genetics
  • Alcoholism / metabolism
  • Alcoholism / pathology
  • Animals
  • Brain / metabolism
  • Brain / pathology*
  • Central Nervous System Depressants / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Ethanol / pharmacology*
  • Female
  • Gene Expression Regulation / drug effects*
  • Genes, Immediate-Early / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar


  • Central Nervous System Depressants
  • Ethanol