title: Exposure to Chronic Mild Stress Differentially Alters Corticotropin-Releasing Hormone and Arginine Vasopressin mRNA Expression in the Stress-Responsive Neurocircuitry of Male and Female Rats Prenatally Exposed to Alcohol.
abstract: BACKGROUND
  Prenatal alcohol exposure (PAE) results in dysregulation of the offspring hypothalamic-pituitary-adrenal (HPA) axis, increasing sensitivity to stressors and vulnerability to stress-related disorders. We have previously shown that exposure to chronic mild stress (CMS) in adulthood significantly increases anxiety-like behaviors (elevated plus maze) in PAE males and females compared to controls. To explore neurobiological mechanisms linking HPA dysregulation and altered anxiety-like behavior, we investigated neuropeptide (corticotropin-releasing hormone [CRH] and arginine vasopressin [AVP]) expression in brain areas involved in the stress neurocircuitry of animals from this previous behavioral study.
  
  
  METHODS
  Adult PAE, pair-fed (PF), and ad libitum fed control (C) male and female offspring exposed to CMS or remaining undisturbed (non-CMS) were terminated 30 minutes following behavioral testing.
  
  
  RESULTS
  In the paraventricular nucleus, CMS increased CRH mRNA levels in PAE compared to PF and C males and increased AVP mRNA levels in PAE compared to C males, with no differential effects for CRH or AVP in females. In the central nucleus of the amygdala, there was an increase in CRH mRNA expression overall, regardless of CMS condition or sex, in PAE compared to C animals. Moreover, in PF males, CMS increased AVP mRNA levels in the paraventricular nucleus, resulting in a decreased CRH/AVP ratio compared to PAE males, and decreased amygdala CRH mRNA compared to that in the non-CMS condition.
  
  
  CONCLUSIONS
  CMS differentially altered central HPA peptide expression in PAE and PF animals compared to their control counterparts, with a possible shift toward greater CRH mediation of HPA regulation in PAE males, and greater AVP mediation of HPA regulation in PF males. However, changes in CRH and AVP expression do not align fully with the anxiogenic profile observed in our previous behavior study, suggesting that other neuronal substrates and limbic forebrain regions also contribute to increased anxiety-like behavior following CMS.
authors.affiliation: Department of Cellular and Physiological Sciences, Faculty of Medicine, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Lan
authors.affiliation: Department of Cellular and Physiological Sciences, Faculty of Medicine, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Psychology, Carleton University, Ottawa, Ontario, Canada.
authors.forename: Kim G C
authors.initials: KG
authors.lastname: Hellemans
authors.affiliation: Department of Cellular and Physiological Sciences, Faculty of Medicine, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Linda
authors.initials: L
authors.lastname: Ellis
authors.affiliation: Department of Cellular and Physiological Sciences, Faculty of Medicine, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Joanne
authors.initials: J
authors.lastname: Weinberg
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001127:Arginine Vasopressin / Q000096:biosynthesis*; D002908:Chronic Disease; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis*; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D005786:Gene Expression Regulation; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology
chemical_list: D012333:RNA, Messenger; D001127:Arginine Vasopressin; D000431:Ethanol; D003346:Corticotropin-Releasing Hormone
keywords: Amygdala; Arginine Vasopressin; Corticotropin-Releasing Hormone; Hypothalamic-Pituitary-Adrenal Axis; Prenatal Alcohol (Ethanol) Exposure