title: Impact of combined prenatal ethanol and prenatal stress exposure on anxiety and hippocampal-sensitive learning in adult offspring.
abstract: BACKGROUND
  Prenatal ethanol (EtOH) and prenatal stress have both been independently shown to induce learning deficits and anxiety behavior in adult offspring. However, the interactive effects of these 2 developmental teratogens on behavioral outcomes have not been systematically evaluated.
  
  
  METHODS
  We combined an established moderate prenatal EtOH consumption paradigm where Long-Evans rat dams voluntarily consume either a 0 or 5% EtOH solution in 0.066% saccharin water (resulting in a mean peak maternal serum EtOH concentration of 84 mg/dl) with a novel prenatal stress paradigm. Pregnant rats were exposed to 3% 2,3,5-trimethyl-3-thiazoline (TMT) for 20 minutes a day on gestational days 13, 15, 17, and 19. Adult female offspring were evaluated for anxiety-like behavior using an elevated plus-maze and hippocampal-sensitive learning using a 2-trial trace conditioning (TTTC) task.
  
  
  RESULTS
  TMT exposure produced a threefold increase in maternal serum corticosterone compared to nonexposed, unhandled controls. Neither prenatal exposure paradigm, either alone or in combination, altered maternal weight gain, EtOH consumption, maternal care of litters, litter size, pup birth weight, or pup weight gain up to weaning. Offspring exposed to prenatal stress displayed significant increases in anxiety-like behavior in the elevated plus maze in terms of open arm entries and time spent on the open arms, with no significant effect of prenatal EtOH exposure and no interaction of the 2 prenatal exposures. Performance in a TTTC task revealed a significant effect of prenatal EtOH exposure on freezing behavior on the testing day, with no significant effect of prenatal stress exposure and no interaction of the 2 prenatal exposures.
  
  
  CONCLUSIONS
  While each prenatal exposure independently produced different behavioral outcomes, the results indicate that there is no significant interaction of prenatal EtOH and prenatal stress exposures on learning or anxiety at the exposure levels employed in this dual exposure paradigm. Subsequent studies will examine whether similar outcomes occur in male offspring and whether other measures of anxiety or learning are differentially impacted by these prenatal exposure paradigms.
authors.affiliation: Department of Neurosciences , University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
authors.forename: Miranda C
authors.initials: MC
authors.lastname: Staples
authors.forename: Martina J
authors.initials: MJ
authors.lastname: Rosenberg
authors.forename: Nyika A
authors.initials: NA
authors.lastname: Allen
authors.forename: Morgan W
authors.initials: MW
authors.lastname: Porch
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Savage
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology*; D001522:Behavior, Animal; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D006624:Hippocampus / Q000503:physiopathology; D007858:Learning; D008297:Male; D018782:Maze Learning; D011247:Pregnancy; D011248:Pregnancy Complications / Q000523:psychology*; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020318:Rats, Long-Evans; D013315:Stress, Psychological / Q000150:complications*
chemical_list: D000431:Ethanol
keywords: Anxiety; Fetal Alcohol Spectrum Disorder; Maternal Stress; Trace Conditioning
references.citation: Nat Neurosci. 2000 Aug;3(8):799-806
references.pmid: 10903573
references.citation: Neurotoxicol Teratol. 2000 Mar-Apr;22(2):143-9
references.pmid: 10758343
references.citation: Alcohol Clin Exp Res. 2010 Oct;34(10):1793-802
references.pmid: 20626729
references.citation: Behav Neurosci. 1997 Apr;111(2):259-66
references.pmid: 9106666
references.citation: Neuroendocrinology. 1996 Dec;64(6):412-8
references.pmid: 8990073
references.citation: Int J Dev Neurosci. 2006 Jun;24(4):255-62
references.pmid: 16698220
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11032-7
references.pmid: 11005874
references.citation: Physiol Behav. 2011 Aug 3;104(2):340-7
references.pmid: 21334352
references.citation: J Neurosci. 1996 Jun 15;16(12):3943-9
references.pmid: 8656288
references.citation: Physiol Behav. 2001 Nov-Dec;74(4-5):435-40
references.pmid: 11790402
references.citation: Eur Neuropsychopharmacol. 1999 Mar;9(3):239-45
references.pmid: 10208294
references.citation: J Int Neuropsychol Soc. 2008 Nov;14(6):1022-33
references.pmid: 18954482
references.citation: Alcohol Clin Exp Res. 1998 May;22(3):685-96
references.pmid: 9622451
references.citation: PLoS One. 2011 Jan 19;6(1):e15982
references.pmid: 21283812
references.citation: Pharmacol Biochem Behav. 2006 Oct;85(2):345-55
references.pmid: 17049371
references.citation: Hippocampus. 2012 Jan;22(1):69-81
references.pmid: 21080406
references.citation: Lancet. 1973 Nov 3;302(7836):999-1001
references.pmid: 4127281
references.citation: J Neurosci Methods. 1985 Aug;14(3):149-67
references.pmid: 2864480
references.citation: Brain Res. 2008 Jun 5;1213:98-110
references.pmid: 18456246
references.citation: Exp Neurol. 2012 Jan;233(1):95-101
references.pmid: 21281632
references.citation: J Neuroendocrinol. 2011 Feb;23(2):118-28
references.pmid: 21108672
references.citation: Pediatr Res. 2004 Sep;56(3):400-10
references.pmid: 15240860
references.citation: Behav Brain Res. 2006 Dec 15;175(2):323-8
references.pmid: 17023059
references.citation: Neuroscience. 2011 Apr 28;180:105-10
references.pmid: 21335068
references.citation: Brain Res. 2007 Apr 13;1141:205-13
references.pmid: 17291462
references.citation: Dev Med Child Neurol. 2003 Mar;45(3):179-82
references.pmid: 12613774
references.citation: J Child Psychol Psychiatry. 2005 Mar;46(3):246-54
references.pmid: 15755301
references.citation: Pediatrics. 2001 Aug;108(2):E34
references.pmid: 11483844
references.citation: Early Hum Dev. 2010 May;86(5):305-10
references.pmid: 20547016
references.citation: Brain Res Dev Brain Res. 2002 Nov 15;139(1):1-8
references.pmid: 12414088
references.citation: Child Dev. 2004 Jan-Feb;75(1):96-109
references.pmid: 15015677
references.citation: J Child Psychol Psychiatry. 2003 Oct;44(7):1025-36
references.pmid: 14531585
references.citation: Dev Disabil Res Rev. 2009;15(3):218-24
references.pmid: 19731385
references.citation: MMWR Morb Mortal Wkly Rep. 2002 Apr 5;51(13):273-6
references.pmid: 11952279
references.citation: Neurotoxicol Teratol. 2004 Mar-Apr;26(2):169-78
references.pmid: 15019951
references.citation: Neuropathol Appl Neurobiol. 1986 May-Jun;12(3):251-60
references.pmid: 3736773
references.citation: Recent Dev Alcohol. 1991;9:95-115
references.pmid: 1758996
references.citation: Neurosci Biobehav Rev. 2012 Jul;36(6):1463-80
references.pmid: 22487135
references.citation: Stress. 2011 Nov;14(6):604-13
references.pmid: 21790452
references.citation: Int J Psychophysiol. 2000 Aug;37(2):195-205
references.pmid: 10832006
references.citation: Am J Psychiatry. 1998 Apr;155(4):552-4
references.pmid: 9546004
references.citation: J Clin Psychiatry. 2006 Aug;67(8):1285-98
references.pmid: 16965210
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2927-32
references.pmid: 19188598
references.citation: J Child Psychol Psychiatry. 2009 Jun;50(6):688-97
references.pmid: 19175817