Sex differences in neuroadaptation to alcohol and withdrawal neurotoxicity

Lynda Sharrett-Field, Tracy R. Butler, Anna R. Reynolds, Jennifer N. Berry, Mark A. Prendergast

Research output: Contribution to journalReview articlepeer-review

56 Scopus citations


Recent work suggests that sex differences exist with regard to both the nature of neuroadaptation to alcohol during the development of dependence, and possibly, the neurodegenerative consequences of alcohol dependence. Volumetric studies in human samples show that females may demonstrate increased volumetric brain loss with equal or lesser dependence histories than males. Furthermore, animal studies demonstrate sex differences in glutamatergic, GABAergic, and adenosinergic receptor signaling and endocrine responses following prolonged alcohol exposure. These differences may influence the development of dependence, neuronal function, and viability, particularly during alcohol withdrawal. The present review discusses the current state of knowledge in this regard. It is concluded that there exists a clear need for a more extensive examination of potential sex differences in neurodegenerative consequences of alcohol dependence in men and women, particularly with regard to the role that alterations in amino acid signaling and hypothalamic-pituitary-adrenal axis function may play. Furthermore, we note the need for expanded examination of the unique role that alcohol withdrawal-associated neuronal activity may have in the development of dependence-associated neurotoxicity.

Original languageEnglish
Pages (from-to)643-654
Number of pages12
JournalPflugers Archiv European Journal of Physiology
Issue number5
StatePublished - May 2013


  • Alcohol dependence
  • Brain
  • Corticosteroid
  • Detoxification
  • Gender
  • Glutamate
  • Hippocampus
  • γ-aminobutyric acid

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)


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