title: Acute alcohol exposure during neurulation: Behavioral and brain structural consequences in adolescent C57BL/6J mice.
abstract: Prenatal alcohol exposure (PAE) can induce physical malformations and behavioral abnormalities that depend in part on thedevelopmental timing of alcohol exposure. The current studies employed a mouse FASD model to characterize the long-term behavioral and brain structural consequences of a binge-like alcohol exposure during neurulation; a first-trimester stage when women are typically unaware that they are pregnant. Time-mated C57BL/6J female mice were administered two alcohol doses (2.8g/kg, four hours apart) or vehicle starting at gestational day 8.0. Male and female adolescent offspring (postnatal day 28-45) were then examined for motor activity (open field and elevated plus maze), coordination (rotarod), spatial learning and memory (Morris water maze), sensory motor gating (acoustic startle and prepulse inhibition), sociability (three-chambered social test), and nociceptive responses (hot plate). Regional brain volumes and shapes were determined using magnetic resonance imaging. In males, PAE increased activity on the elevated plus maze and reduced social novelty preference, while in females PAE increased exploratory behavior in the open field and transiently impaired rotarod performance. In both males and females, PAE modestly impaired Morris water maze performance and decreased the latency to respond on the hot plate. There were no brain volume differences; however, significant shape differences were found in the cerebellum, hypothalamus, striatum, and corpus callosum. These results demonstrate that alcohol exposure during neurulation can have functional consequences into adolescence, even in the absence of significant brain regional volumetric changes. However, PAE-induced regional shape changes provide evidence for persistent brain alterations and suggest alternative clinical diagnostic markers.
authors.affiliation: Bowles Center for Alcohol Studies (EWF, HTH, LKB, LAW, SEP), Department of Cell Biology and Physiology (SEP), Department of Psychiatry (AMR, SSM, BP), and Carolina Institute for Developmental Disabilities (SSM, BP, SEP), University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: E W
authors.initials: EW
authors.lastname: Fish
authors.affiliation: Bowles Center for Alcohol Studies (EWF, HTH, LKB, LAW, SEP), Department of Cell Biology and Physiology (SEP), Department of Psychiatry (AMR, SSM, BP), and Carolina Institute for Developmental Disabilities (SSM, BP, SEP), University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: H T
authors.initials: HT
authors.lastname: Holloway
authors.affiliation: Bowles Center for Alcohol Studies (EWF, HTH, LKB, LAW, SEP), Department of Cell Biology and Physiology (SEP), Department of Psychiatry (AMR, SSM, BP), and Carolina Institute for Developmental Disabilities (SSM, BP, SEP), University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: A
authors.initials: A
authors.lastname: Rumple
authors.affiliation: Bowles Center for Alcohol Studies (EWF, HTH, LKB, LAW, SEP), Department of Cell Biology and Physiology (SEP), Department of Psychiatry (AMR, SSM, BP), and Carolina Institute for Developmental Disabilities (SSM, BP, SEP), University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: L K
authors.initials: LK
authors.lastname: Baker
authors.affiliation: Bowles Center for Alcohol Studies (EWF, HTH, LKB, LAW, SEP), Department of Cell Biology and Physiology (SEP), Department of Psychiatry (AMR, SSM, BP), and Carolina Institute for Developmental Disabilities (SSM, BP, SEP), University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: L A
authors.initials: LA
authors.lastname: Wieczorek
authors.affiliation: Bowles Center for Alcohol Studies (EWF, HTH, LKB, LAW, SEP), Department of Cell Biology and Physiology (SEP), Department of Psychiatry (AMR, SSM, BP), and Carolina Institute for Developmental Disabilities (SSM, BP, SEP), University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: S S
authors.initials: SS
authors.lastname: Moy
authors.affiliation: Bowles Center for Alcohol Studies (EWF, HTH, LKB, LAW, SEP), Department of Cell Biology and Physiology (SEP), Department of Psychiatry (AMR, SSM, BP), and Carolina Institute for Developmental Disabilities (SSM, BP, SEP), University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: B
authors.initials: B
authors.lastname: Paniagua
authors.affiliation: Bowles Center for Alcohol Studies (EWF, HTH, LKB, LAW, SEP), Department of Cell Biology and Physiology (SEP), Department of Psychiatry (AMR, SSM, BP), and Carolina Institute for Developmental Disabilities (SSM, BP, SEP), University of North Carolina, Chapel Hill, NC 27599, United States. Electronic address: sparnell@med.unc.edu.
authors.forename: S E
authors.initials: SE
authors.lastname: Parnell
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000254:growth & development*; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000000981:diagnostic imaging*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008810:Mice, Inbred C57BL; D054261:Neurulation / Q000187:drug effects*; D009929:Organ Size; D017288:Pain Threshold / Q000187:drug effects; D065808:Prepulse Inhibition / Q000187:drug effects; D012737:Sex Factors; D012919:Social Behavior
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol
keywords: Behavior; Brain; Ethanol; Fetal alcohol spectrum disorder; Mouse