Effects of chronic alcohol consumption and withdrawal on the response of the male and female hypothalamic-pituitary-adrenal axis to acute immune stress

Brain Res. 2012 Mar 20;1444:27-37. doi: 10.1016/j.brainres.2012.01.013. Epub 2012 Jan 25.

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the response to stress, and its activity is sexually dimorphic and modulated by sex steroids. Recent work indicates that HPA axis functioning is disturbed by chronic alcohol consumption and subsequent withdrawal in rats of both sexes, but particularly in females. To examine the influence of sex steroid hormones in HPA axis response to acute stress after ingestion of a 20% ethanol solution over 6months and subsequent withdrawal (2months), intact males, and estradiol- and oil-injected ovariectomized females received a single intraperitoneal injection of lipopolysaccharide (LPS). Six hours after LPS administration, corticosterone concentrations were increased in all male groups; however, in ethanol-treated rats they remained below those of control and withdrawn rats. mRNA levels of corticotrophin-releasing hormone (CRH) increased, and were identical in all groups after LPS stimulation, whereas those of vasopressin, although increased, remained below control levels. LPS stimulation elevated corticosterone concentrations in all oil-injected female groups, but did not alter those of estradiol-injected females. In oil- and estradiol-injected ethanol-treated females, CRH mRNA levels did not change in response to LPS stimulation, whereas those of vasopressin increased, but stayed below control levels. In withdrawn oil- and estradiol-injected females, CRH and vasopressin gene expression increased, but did not reach control levels. These data show that prolonged alcohol consumption produces long-lasting, possibly irreversible, changes in the neuroendocrine system that regulates the production of corticosteroids, and that these consequences are more profound in females, particularly when estrogen levels are low.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / pathology*
  • Animals
  • Corticosterone / metabolism
  • Corticotropin-Releasing Hormone / genetics
  • Corticotropin-Releasing Hormone / metabolism
  • Disease Models, Animal
  • Estradiol / pharmacology
  • Ethanol / adverse effects*
  • Ethanol / pharmacology
  • Female
  • Gene Expression Regulation / drug effects
  • Histamine H1 Antagonists
  • Hypothalamo-Hypophyseal System / drug effects*
  • Hypothalamo-Hypophyseal System / metabolism
  • Lipopolysaccharides / pharmacology
  • Male
  • Ovariectomy
  • Pituitary-Adrenal System / drug effects*
  • Pituitary-Adrenal System / metabolism
  • Promethazine
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Sex Characteristics*
  • Substance Withdrawal Syndrome / pathology*
  • Time Factors
  • Vasopressins / metabolism

Substances

  • Histamine H1 Antagonists
  • Lipopolysaccharides
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Vasopressins
  • Ethanol
  • Estradiol
  • Corticotropin-Releasing Hormone
  • Promethazine
  • Corticosterone