title: Neonatal Ethanol Exposure Impairs Trace Fear Conditioning and Alters NMDA Receptor Subunit Expression in Adult Male and Female Rats.
abstract: BACKGROUND
  Ethanol (EtOH) exposure in neonate rats during a period comparable to the human third trimester, postnatal days (PD) 4 to 9, leads to persistent deficits in forebrain-dependent cognitive function--modeling the dysfunction seen in individuals diagnosed with fetal alcohol spectrum disorders. EtOH-exposed adult rats are impaired in auditory trace fear conditioning (TFC), a form of Pavlovian conditioning in which a neutral conditioned stimulus (CS; tone) is followed by an aversive unconditioned stimulus (US; footshock), with both stimuli separated in time by a stimulus-free "trace" interval (TI). TFC acquisition depends on N-methyl-d-aspartate NMDA receptor (NMDAR) activation in the dorsal hippocampus (DH), ventral hippocampus (VH), and medial prefrontal cortex (mPFC).
  
  
  METHODS
  Male and female rat pups were sham-intubated (SI) or intragastrically intubated with EtOH (5E; 5 g/kg/d) over PD 4 to 9 and, as adults, submitted to TFC with a 15-second tone CS and 30-second TI. Whole-cell tissue lysates from the DH, VH, and mPFC of TFC rats and DH synaptic/extrasynaptic membrane fractions from experimentally naïve animals were analyzed via Western blot for NMDAR subunit (GluN1, GluN2A, GluN2B) expression.
  
  
  RESULTS
  Freezing behavior during CS-alone test trials was significantly reduced in both male and female 5E rats, relative to same-sex controls. Western blot results based on DH tissue samples revealed a greater proportion of GluN2A to GluN2B subunits in 5E rats, relative to SI rats, and significantly reduced synaptic GluN2B and PSD-95 expression.
  
  
  CONCLUSIONS
  EtOH-induced changes in DH NMDAR subunit expression-particularly synaptic GluN2B, which is critical for TFC-are proposed to weaken long-term memory consolidation and, during behavioral testing, diminish CS-evoked freezing behavior.
authors: Department of Psychology, The Ohio State University, Columbus, Ohio.
authors: Molly J
authors: MJ
authors: Goodfellow
authors: Department of Psychology, The Ohio State University, Columbus, Ohio.|Department of Neuroscience, The Ohio State University, Columbus, Ohio.
authors: Khalid A
authors: KA
authors: Abdulla
authors: Department of Psychology, The Ohio State University, Columbus, Ohio.|Department of Neuroscience, The Ohio State University, Columbus, Ohio.
authors: Derick H
authors: DH
authors: Lindquist
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D003214:Conditioning, Classical / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects*; D005260:Female; D006624:Hippocampus / Q000737:chemistry; D008297:Male; D017397:Prefrontal Cortex / Q000737:chemistry; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000187:drug effects*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol
keywords: Fetal Alcohol Spectrum Disorders; Hippocampus; Memory Consolidation; NMDA Receptors; Trace Fear Conditioning