Abstract
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.
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Acknowledgments
This project was supported by National Institute on Alcohol Abuse and Alcoholism Grant AA021637 awarded to T. Retson, and National Institute on Drug Abuse Grant DA009082 and DA020129 awarded to E. Van Bockstaele. The authors would also like to thank Dr. Jed Shumsky for his statistical expertise, Brian Corbett for his assistance with ΔFosB, Krista Connelly, Jessica Sterling, and Scott Dougherty for their experimental assistance, Robert Lybek for his perspective, Diane Stringer, N. R., Leela Doge, M. A. Rubel, and Jeff Yost for their ongoing discourse and support.
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Retson, T.A., Hoek, J.B., Sterling, R.C. et al. Amygdalar neuronal plasticity and the interactions of alcohol, sex, and stress. Brain Struct Funct 220, 3211–3232 (2015). https://doi.org/10.1007/s00429-014-0851-4
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DOI: https://doi.org/10.1007/s00429-014-0851-4