Send to

Choose Destination
Brain Struct Funct. 2015 Nov;220(6):3211-32. doi: 10.1007/s00429-014-0851-4. Epub 2014 Aug 1.

Amygdalar neuronal plasticity and the interactions of alcohol, sex, and stress.

Author information

Department of Neuroscience, Farber Institute for Neurosciences, Thomas Jefferson University, 900 Walnut Street, Suite 417, Philadelphia, PA, 19107, USA.
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Department of Psychiatry, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Department of Pharmacology and Physiology, Drexel University, Philadelphia, PA, 19107, USA.


Alcohol abuse and alcoholism are major medical problems affecting both men and women. Previous animal studies reported a difference in c-Fos neuronal activation after chronic alcohol exposure; however, females remain an understudied population. To model chronic alcohol exposure match-pair fed adult male and female rats were administered 14 days of a liquid ethanol containing diet. Analysis focused on the central nucleus of the amygdala (CeA), a region integral to stress sensitivity and substance abuse. Immunocytochemical approaches identified cells containing ΔFosB, a marker of sustained neuronal activation, and activity patterns within the CeA were mapped by subdivision and rostral-caudal extent. Significant interactions were present between all groups, with gender differences noted among control groups, and ethanol exposed animals having the greatest number of ΔFosB immunoreactive cells indicating baseline dysregulation. Compared with c-Fos, a marker of recent neuronal activation, male ethanol treated animals had similar activity to controls, indicating a neuronal habituation not seen in females. Next, a cohort of animals were exposed to the forced swim test (FST), and c-Fos was examined in addition to FST behavior. Neuronal activity was increased in ethanol exposed animals compared to controls, and control females compared to males, indicating a potentiated stress response. Further, a population of activated neurons were shown to contain either corticotropin releasing factor or enkephalin. The present data suggest that dysregulation in the CeA neuronal activity may underlie some of the negative sequelae of alcohol abuse, and may, in part, underlie the distinctive response seen between genders to alcohol use.


Central nucleus of the amygdala; Chronic alcohol; Sex differences; c-Fos; ΔFosB

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center