Examination of age-dependent effects of fetal ethanol exposure on behavior, hippocampal cell counts, and doublecortin immunoreactivity in rats

Dev Neurobiol. 2014 May;74(5):498-513. doi: 10.1002/dneu.22143. Epub 2013 Dec 3.


Ethanol is known as a potent teratogen having adverse effects on brain and behavior. However, some of the behavioral deficits caused by fetal alcohol exposure and well expressed in juveniles ameliorate with maturation may suggest some kind of functional recovery occurring during postnatal development. The aim of this study was to reexamine age-dependent behavioral impairments in fetal-alcohol rats and to investigate the changes in neurogenesis and gross morphology of the hippocampus during a protracted postnatal period searching for developmental deficits and/or delays that would correlate with behavioral impairments in juveniles and for potential compensatory processes responsible for their amelioration in adults. Ethanol was delivered to the pregnant dams by intragastric intubation throughout 7-21 gestation days at daily dose of 6 g/kg. Isocaloric intubation and intact control groups were included. Locomotor activity, anxiety, and spatial learning tasks were applied to juvenile and young-adult rats from all groups. Unbiased stereological estimates of hippocampal volumes, the total number of pyramidal and granular cells, and double cortin expressing neurons were carried out for postnatal days (PDs) PD1, PD10, PD30, and PD60. Alcohol insult during second trimester equivalent caused significant deficits in the spatial learning in juvenile rats; however, its effect on hippocampal morphology was limited to a marginally lower number of granular cells in dentate gyrus (DG) on PD30. Thus, initial behavioral deficits and the following functional recovery in fetal-alcohol subjects may be due to more subtle plastic changes within the hippocampal formation but also in other structures of the extended hippocampal circuit. Further investigation is required.

Keywords: doublecortin immunoreactivity; fetal alcohol; postnatal hippocampal development; rat; unbiased stereology.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Cell Count
  • Central Nervous System Depressants / adverse effects
  • Ethanol / toxicity*
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Female
  • Fetal Alcohol Spectrum Disorders / pathology*
  • Fetal Alcohol Spectrum Disorders / physiopathology*
  • Hippocampus / drug effects
  • Hippocampus / growth & development
  • Hippocampus / pathology*
  • Hippocampus / physiopathology*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Microtubule-Associated Proteins / metabolism
  • Neurogenesis / drug effects
  • Neurogenesis / physiology
  • Neurons / drug effects
  • Neurons / pathology
  • Neurons / physiology
  • Neuropeptides / metabolism
  • Organ Size
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / growth & development
  • Pyramidal Cells / pathology
  • Pyramidal Cells / physiology
  • Rats, Wistar


  • Central Nervous System Depressants
  • Microtubule-Associated Proteins
  • Neuropeptides
  • doublecortin protein
  • Ethanol