title: Hypothalamic-pituitary-adrenal axis and behavioral dysfunction following early binge-like prenatal alcohol exposure in mice.
abstract: The range of defects that fall within fetal alcohol spectrum disorder (FASD) includes persistent behavioral problems, with anxiety and depression being two of the more commonly reported issues. Previous studies of rodent FASD models suggest that interference with hypothalamic-pituitary-adrenal (HPA) axis structure and/or function may be the basis for some of the prenatal alcohol (ethanol) exposure (PAE)-induced behavioral abnormalities. Included among the previous investigations are those illustrating that maternal alcohol treatment limited to very early stages of pregnancy (i.e., gestational day [GD]7 in mice; equivalent to the third week post-fertilization in humans) can cause structural abnormalities in areas such as the hypothalamus, pituitary gland, and other forebrain regions integral to controlling stress and behavioral responses. The current investigation was designed to further examine the sequelae of prenatal alcohol insult at this early time period, with particular attention to HPA axis-associated functional changes in adult mice. The results of this study reveal that GD7 PAE in mice causes HPA axis dysfunction, with males and females showing elevated corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, respectively, following a 15-min restraint stress exposure. Males also showed elevated CORT levels following an acute alcohol injection of 2.0 g/kg, while females displayed blunted ACTH levels. Furthermore, analysis showed that anxiety-like behavior was decreased after GD7 PAE in female mice, but was increased in male mice. Collectively, the results of this study show that early gestational alcohol exposure in mice alters long-term HPA axis activity and behavior in a sexually dimorphic manner.
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA. Electronic address: lawieczo@med.unc.edu.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Wieczorek
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Fish
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA; Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Shonagh K
authors.initials: SK
authors.lastname: O'Leary-Moore
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA; Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA; Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Parnell
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA; Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA; Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Sulik
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D063425:Binge Drinking; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003345:Corticosterone / Q000378:metabolism*; D003863:Depression / Q000378:metabolism / Q000523:psychology; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism / Q000523:psychology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000523:psychology; D012149:Restraint, Physical; D012737:Sex Factors; D013315:Stress, Psychological / Q000378:metabolism / Q000523:psychology
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
keywords: Anxiety; Depression; FASD; Hypothalamic-pituitary-adrenal axis; Prenatal alcohol exposure; Stress