Skip to main content

Animal Models of Fetal Alcohol Spectrum Disorder

  • Protocol
Animal Models of Neurodevelopmental Disorders

Part of the book series: Neuromethods ((NM,volume 104))

Abstract

This chapter reviews the development and use of animal models in research on Fetal Alcohol Spectrum Disorder, highlighting methodological issues. The development of suitable animal models in this field has been crucial in investigating the wide range of effects of prenatal alcohol exposure under tightly controlled conditions, as well as factors that can influence the severity of effects observed, and the mechanisms mediating those effects. Animal models in this field have been critical in demonstrating that alcohol is a powerful teratogen with serious neurodevelopmental consequences, a fact that was met with skepticism by many in the scientific community when Fetal Alcohol Syndrome was first described. The review begins with a discussion of the various animal models in the field, highlighting the benefits and limitations of each model. Although it is not inclusive, this chapter aims to provide an overview of the challenges that FASD researchers have had in developing animal models that have construct, face and etiological validity. We then discuss the factors that must be addressed in the development of an animal model, including dose and timing of alcohol exposure, blood alcohol levels (BALs), mode of alcohol administration, nutritional considerations, maternal–pup interactions, housing considerations, and strain differences. The chapter then moves on to discuss in some detail the model of chronic, moderate prenatal alcohol exposure utilized in our research with Sprague–Dawley rats. A detailed discussion of our breeding, feeding, culling, and weaning procedures is provided, including the specifics of our liquid diets and feeding schedule, with particular consideration of the issue of pair-feeding. Finally, detailed notes are provided to explain the rationale underlying methodology and procedures described in our protocol.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Lemoine P et al (1968) Children of alcoholic parents: abnormalities observed in 127 cases. Ouest Med 8:476–482

    Google Scholar 

  2. Jones K, Smith D (1973) Recognition of the fetal alcohol syndrome in early infancy. Lancet 2:999–1001

    Google Scholar 

  3. Davis J, Li Y, Rankin C (2008) Effects of developmental exposure to ethanol on Caenorhabditis elegans. Alcohol Clin Exp Res 32(5):853–867

    CAS  PubMed  Google Scholar 

  4. McClure KD, French RL, Heberlein U (2011) A Drosophila model for fetal alcohol syndrome disorders: role for the insulin pathway. Dis Model Mech 4(3):335–346

    PubMed Central  CAS  PubMed  Google Scholar 

  5. Bilotta J et al (2002) Effects of embryonic exposure to ethanol on zebrafish visual function. Neurotoxicol Teratol 24(6):759–766

    CAS  PubMed  Google Scholar 

  6. Ellis FW, Pick JR (1980) An animal model of the fetal alcohol syndrome in beagles. Alcohol Clin Exp Res 4(2):123–134

    CAS  PubMed  Google Scholar 

  7. Lafond JS et al (1985) Effects of maternal alcohol intoxication on fetal circulation and myocardial function: an experimental study in the ovine fetus. J Pediatr 107(6):947–950

    CAS  PubMed  Google Scholar 

  8. Lochry EA et al (1982) Effects of acute alcohol exposure during selected days of gestation in C3H mice. Neurobehav Toxicol Teratol 4(1):15–19

    CAS  PubMed  Google Scholar 

  9. West JR et al (1984) Prenatal and early postnatal exposure to ethanol permanently alters the rat hippocampus. Ciba Found Symp 105:8–25

    CAS  PubMed  Google Scholar 

  10. Weinberg J, Nelson LR, Taylor AN (1986) Hormonal effects of fetal alcohol exposure. In: West J (ed) Alcohol and brain development. Oxford University Press, New York, NY, pp 310–342

    Google Scholar 

  11. Dobson CC et al (2012) Sensitivity of modified Biel-maze task, compared with Y-maze task, to measure spatial learning and memory deficits of ethanol teratogenicity in the guinea pig. Behav Brain Res 233(1):162–168

    CAS  PubMed  Google Scholar 

  12. Abdollah S, Brien JF (1995) Effect of chronic maternal ethanol administration on glutamate and N-methyl-D-aspartate binding sites in the hippocampus of the near-term fetal guinea pig. Alcohol 12(4):377–382

    CAS  PubMed  Google Scholar 

  13. Altshuler HL, Shippenberg TS (1981) A subhuman primate model for fetal alcohol syndrome research. Neurobehav Toxicol Teratol 3(2):121–126

    CAS  PubMed  Google Scholar 

  14. Clarren SK, Bowden DM (1982) Fetal alcohol syndrome: a new primate model for binge drinking and its relevance to human ethanol teratogenesis. J Pediatr 101(5):819–824

    CAS  PubMed  Google Scholar 

  15. Fisher SE et al (1983) Selective fetal malnutrition: the effect of in vivo ethanol exposure upon in vitro placental uptake of amino acids in the non-human primate. Pediatr Res 17(9):704–707

    CAS  PubMed  Google Scholar 

  16. Heaton MB et al (1992) Ethanol exposure affects trophic factor activity and responsiveness in chick embryo. Alcohol 9(2):161–166

    CAS  PubMed  Google Scholar 

  17. Lockwood B et al (2004) Acute effects of alcohol on larval zebrafish: a genetic system for large-scale screening. Pharmacol Biochem Behav 77(3):647–654

    CAS  PubMed  Google Scholar 

  18. Means LW, Burnette MA, Pennington SN (1988) The effect of embryonic ethanol exposure on detour learning in the chick. Alcohol 5(4):305–308

    CAS  PubMed  Google Scholar 

  19. Gerlai R (2003) Zebra fish: an uncharted behavior genetic model. Behav Genet 33(5):461–468

    PubMed  Google Scholar 

  20. Su B et al (2001) Genetic influences on craniofacial outcome in an avian model of prenatal alcohol exposure. Alcohol Clin Exp Res 25(1):60–69

    CAS  PubMed  Google Scholar 

  21. Ahlgren SC, Bronner-Fraser M (1999) Inhibition of sonic hedgehog signaling in vivo results in craniofacial neural crest cell death. Curr Biol 9(22):1304–1314

    CAS  PubMed  Google Scholar 

  22. Morgan PG, Sedensky MM (1995) Mutations affecting sensitivity to ethanol in the nematode, Caenorhabditis elegans. Alcohol Clin Exp Res 19(6):1423–1429

    CAS  PubMed  Google Scholar 

  23. Randall CL, Ekblad U, Anton RF (1990) Perspectives on the pathophysiology of fetal alcohol syndrome. Alcohol Clin Exp Res 14(6):807–812

    CAS  PubMed  Google Scholar 

  24. Goodlett CR, Horn KH, Zhou FC (2005) Alcohol teratogenesis: mechanisms of damage and strategies for intervention. Exp Biol Med (Maywood) 230(6):394–406

    CAS  Google Scholar 

  25. Zhang X, Sliwowska JH, Weinberg J (2005) Prenatal alcohol exposure and fetal programming: effects on neuroendocrine and immune function. Exp Biol Med (Maywood) 230(6):376–388

    CAS  Google Scholar 

  26. Hellemans KG et al (2010) Prenatal alcohol exposure: fetal programming and later life vulnerability to stress, depression and anxiety disorders. Neurosci Biobehav Rev 34(6):791–807

    CAS  PubMed  Google Scholar 

  27. Webster WS et al (1980) Teratogenesis after acute alcohol exposure in inbred and outbred mice. Neurobehav Toxicol 2(3):227–234

    CAS  Google Scholar 

  28. Sulik KK, Johnston MC (1983) Sequence of developmental alterations following acute ethanol exposure in mice - craniofacial features of the fetal alcohol syndrome. Am J Anat 166(3):257–269

    CAS  PubMed  Google Scholar 

  29. Sulik KK, Schoenwolf GC (1985) Highlights of craniofacial morphogenesis in mammalian embryos, as revealed by scanning electron-microscopy. Scan Electron Microsc (Pt 4):1735–1752

    Google Scholar 

  30. Sinden JD, Le Magnen J (1982) Parameters of low-dose ethanol intravenous self-administration in the rat. Pharmacol Biochem Behav 16(1):181–183

    CAS  PubMed  Google Scholar 

  31. Dobbing J, Sands J (1979) Comparative aspects of the brain growth spurt. Early Hum Dev 3(1):79–83

    CAS  PubMed  Google Scholar 

  32. Kimura S et al (1985) Immunoregulation in the rat: ontogeny of B cell responses to types 1, 2, and T-dependent antigens. J Immunol 134(5):2839–2846

    CAS  PubMed  Google Scholar 

  33. Gottesfeld Z, LeGrue SJ (1990) Lactational alcohol exposure elicits long-term immune deficits and increased noradrenergic synaptic transmission in lymphoid organs. Life Sci 47(5):457–465

    CAS  PubMed  Google Scholar 

  34. Mennella J (2001) Alcohol’s effect on lactation. Alcohol Res Health 25(3):230–234

    CAS  PubMed  Google Scholar 

  35. Pepino MY et al (2002) Disruption of maternal behavior by alcohol intoxication in the lactating rat: a behavioral and metabolic analysis. Alcohol Clin Exp Res 26(8):1205–1214

    CAS  PubMed  Google Scholar 

  36. West JR (1993) Use of pup in a cup model to study brain development. J Nutr 123(2 Suppl):382–385

    CAS  PubMed  Google Scholar 

  37. Goodlett CR, Johnson TB (1997) Neonatal binge ethanol exposure using intubation: timing and dose effects on place learning. Neurotoxicol Teratol 19(6):435–446

    CAS  PubMed  Google Scholar 

  38. Levine S (1967) Maternal and environmental influences on the adrenocortical response to stress in weanling rats. Science 156(772):258–260

    CAS  PubMed  Google Scholar 

  39. Idanpaan-Heikkila J et al (1972) Elimination and metabolic effects of ethanol in mother, fetus, and newborn infant. Am J Obstet Gynecol 112(3):387–393

    CAS  PubMed  Google Scholar 

  40. Meier-Tackmann D et al (1985) Human placental aldehyde dehydrogenase. Subcellular distribution and properties. Enzyme 33(3):153–161

    CAS  PubMed  Google Scholar 

  41. Burd L et al (2007) Ethanol and the placenta: a review. J Matern Fetal Neonatal Med 20(5):361–375

    CAS  PubMed  Google Scholar 

  42. Karl PI et al (1988) Acetaldehyde production and transfer by the perfused human placental cotyledon. Science 242(4876):273–275

    CAS  PubMed  Google Scholar 

  43. Anderson RA Jr (1981) Endocrine balance as a factor in the etiology of the fetal alcohol syndrome. Neurobehav Toxicol Teratol 3(2):89–104

    CAS  PubMed  Google Scholar 

  44. Sliwowska J, Zhang X, Weinberg J (2006) Prenatal ethanol exposure and fetal programming: implications for endocrine and immune development and long-term health. In: Miller MW (ed) Brain development: normal processes and the effects of alcohol and nicotine. Oxford University Press, Oxford [u.a.]

    Google Scholar 

  45. Gallo PV, Weinberg J (1986) Organ growth and cellular development in ethanol-exposed rats. Alcohol 3(4):261–267

    CAS  PubMed  Google Scholar 

  46. Weinberg J (1989) Prenatal ethanol exposure alters adrenocortical development of offspring. Alcohol Clin Exp Res 13(1):73–83

    CAS  PubMed  Google Scholar 

  47. Driscoll CD, Streissguth AP, Riley EP (1990) Prenatal alcohol exposure: comparability of effects in humans and animal models. Neurotoxicol Teratol 12(3):231–237

    CAS  PubMed  Google Scholar 

  48. Chernoff GF (1977) The fetal alcohol syndrome in mice: an animal model. Teratology 15(3):223–229

    CAS  PubMed  Google Scholar 

  49. Randall CL, Taylor WJ (1979) Prenatal ethanol exposure in mice: teratogenic effects. Teratology 19(3):305–311

    CAS  PubMed  Google Scholar 

  50. West JR, Kelly SJ, Pierce DR (1987) Severity of alcohol-induced deficits in rats during the third trimester equivalent is determined by the pattern of exposure. Alcohol Alcohol Suppl 1:461–465

    CAS  PubMed  Google Scholar 

  51. West JR et al (1989) Manipulating peak blood alcohol concentrations in neonatal rats: review of an animal model for alcohol-related developmental effects. Neurotoxicology 10(3):347–365

    CAS  PubMed  Google Scholar 

  52. Pierce DR, West JR (1986) Blood alcohol concentration: a critical factor for producing fetal alcohol effects. Alcohol 3(4):269–272

    CAS  PubMed  Google Scholar 

  53. Pierce DR, West JR (1986) Alcohol-induced microencephaly during the third trimester equivalent: relationship to dose and blood alcohol concentration. Alcohol 3(3):185–191

    CAS  PubMed  Google Scholar 

  54. Bonthius DJ, West JR (1988) Blood alcohol concentration and microencephaly: a dose-response study in the neonatal rat. Teratology 37(3):223–231

    CAS  PubMed  Google Scholar 

  55. Maier SE, West JR (2001) Drinking patterns and alcohol-related birth defects. Alcohol Res Health 25(3):168–174

    CAS  PubMed  Google Scholar 

  56. Dole VP, Ho A, Gentry RT (1985) Toward an analogue of alcoholism in mice: criteria for recognition of pharmacologically motivated drinking. Proc Natl Acad Sci U S A 82(10):3469–3471

    PubMed Central  CAS  PubMed  Google Scholar 

  57. Crabbe JC et al (2009) A line of mice selected for high blood ethanol concentrations shows drinking in the dark to intoxication. Biol Psychiatry 65(8):662–670

    PubMed Central  CAS  PubMed  Google Scholar 

  58. Carelli RM (2002) The nucleus accumbens and reward: neurophysiological investigations in behaving animals. Behav Cogn Neurosci Rev 1(4):281–296

    PubMed  Google Scholar 

  59. Frazier CR et al (2008) Sucrose exposure in early life alters adult motivation and weight gain. PLoS One 3(9):e3221

    PubMed Central  PubMed  Google Scholar 

  60. Roman E et al (2012) Behavioral profiling of multiple pairs of rats selectively bred for high and low alcohol intake using the MCSF test. Addict Biol 17:33

    CAS  PubMed  Google Scholar 

  61. Colombo G et al (2006) Phenotypic characterization of genetically selected Sardinian alcohol-preferring (sP) and -non-preferring (sNP) rats. Addict Biol 11(3–4):324–338

    PubMed  Google Scholar 

  62. Sinclair JD, Le AD, Kiianmaa K (1989) The AA and ANA rat lines, selected for differences in voluntary alcohol consumption. Experientia 45(9):798–805

    CAS  PubMed  Google Scholar 

  63. Riley EP et al (1993) Alterations in activity following alcohol administration during the third trimester equivalent in P and NP rats. Alcohol Clin Exp Res 17(6):1240–1246

    CAS  PubMed  Google Scholar 

  64. Hamilton DA et al (2010) Prenatal exposure to moderate levels of ethanol alters social behavior in adult rats: relationship to structural plasticity and immediate early gene expression in frontal cortex. Behav Brain Res 207(2):290–304

    PubMed Central  CAS  PubMed  Google Scholar 

  65. Hamilton DA et al (2010) Patterns of social-experience-related c-fos and Arc expression in the frontal cortices of rats exposed to saccharin or moderate levels of ethanol during prenatal brain development. Behav Brain Res 214(1):66–74

    PubMed Central  CAS  PubMed  Google Scholar 

  66. Savage DD et al (2002) Dose-dependent effects of prenatal ethanol exposure on synaptic plasticity and learning in mature offspring. Alcohol Clin Exp Res 26(11):1752–1758

    PubMed  Google Scholar 

  67. Wiener SG et al (1981) Interaction of ethanol and nutrition during gestation: influence on maternal and offspring development in the rat. J Pharmacol Exp Ther 216(3):572–579

    CAS  PubMed  Google Scholar 

  68. Dexter JD et al (1976) Sinclair(S-1) miniature swine as a model for the study of human alcoholism. Ann N Y Acad Sci 273:188–193

    CAS  PubMed  Google Scholar 

  69. Riley EP, Meyer LS (1984) Considerations for the design, implementation, and interpretation of animal models of fetal alcohol effects. Neurobehav Toxicol Teratol 6(2):97–101

    CAS  PubMed  Google Scholar 

  70. Burke MW et al (2009) Neuronal reduction in frontal cortex of primates after prenatal alcohol exposure. Neuroreport 20(1):13–17

    PubMed  Google Scholar 

  71. Lee S et al (1990) Effect of prenatal exposure to ethanol on the activity of the hypothalamic-pituitary-adrenal axis of the offspring: importance of the time of exposure to ethanol and possible modulating mechanisms. Mol Cell Neurosci 1(2):168–177

    CAS  PubMed  Google Scholar 

  72. Kang SS et al (2004) Development of individual alcohol inhalation chambers for mice: validation in a model of prenatal alcohol. Alcohol Clin Exp Res 28(10):1549–1556

    PubMed  Google Scholar 

  73. Lieber CS, DeCarli LM, Sorrell MF (1989) Experimental methods of ethanol administration. Hepatology 10(4):501–510

    CAS  PubMed  Google Scholar 

  74. Ponnappa BC, Rubin E (2000) Modeling alcohol’s effects on organs in animal models. Alcohol Res Health 24(2):93–104

    CAS  PubMed  Google Scholar 

  75. Sugino N et al (1994) Effects of restraint stress on luteal function in rats during mid-pregnancy. J Reprod Fertil 101(1):23–26

    Google Scholar 

  76. Grant KA, Samson HH (1985) Oral self administration of ethanol in free feeding rats. Alcohol 2(2):317–321

    CAS  PubMed  Google Scholar 

  77. Grant KA, Samson HH (1985) Induction and maintenance of ethanol self-administration without food deprivation in the rat. Psychopharmacology (Berl) 86(4):475–479

    CAS  Google Scholar 

  78. Samson HH, Falk JL (1974) Schedule-induced ethanol polydipsia: enhancement by saccharin. Pharmacol Biochem Behav 2(6):835–838

    CAS  PubMed  Google Scholar 

  79. Meisch RA, Thompson T (1972) Ethanol intake during schedule-induced polydipsia. Physiol Behav 8(3):471–475

    CAS  PubMed  Google Scholar 

  80. Weinberg J (1984) Nutritional issues in perinatal alcohol exposure. Neurobehav Toxicol Teratol 6(4):261–269

    CAS  PubMed  Google Scholar 

  81. Sherwin BT, Jacobson S, Zagorski D (1981) A rat model of the fetal alcohol syndrome – preliminary histological findings. Curr Alcohol 8:495–510

    CAS  PubMed  Google Scholar 

  82. Lieber CS, DeCarli LM (1989) Liquid diet technique of ethanol administration: 1989 update. Alcohol Alcohol 24(3):197–211

    CAS  PubMed  Google Scholar 

  83. Lieber CS, DeCarli LM (1982) The feeding of alcohol in liquid diets: two decades of applications and 1982 update. Alcohol Clin Exp Res 6(4):523–531

    CAS  PubMed  Google Scholar 

  84. George FR (1987) Genetic and environmental factors in ethanol self-administration. Pharmacol Biochem Behav 27(2):379–384

    CAS  PubMed  Google Scholar 

  85. Weinberg J (1985) Effects of ethanol and maternal nutritional status on fetal development. Alcohol Clin Exp Res 9(1):49–55

    CAS  PubMed  Google Scholar 

  86. Glavas MM et al (2007) Effects of prenatal ethanol exposure on basal limbic-hypothalamic-pituitary-adrenal regulation: role of corticosterone. Alcohol Clin Exp Res 31(9):1598–1610

    CAS  PubMed  Google Scholar 

  87. Hofmann C et al (1999) Glucocorticoid fast feedback is not altered in rats prenatally exposed to ethanol. Alcohol Clin Exp Res 23(5):891–900

    CAS  PubMed  Google Scholar 

  88. Gallo PV, Weinberg J (1981) Corticosterone rhythmicity in the rat: interactive effects of dietary restriction and schedule of feeding. J Nutr 111(2):208–218

    CAS  PubMed  Google Scholar 

  89. Weinberg J, Gallo PV (1982) Prenatal ethanol exposure: pituitary-adrenal activity in pregnant dams and offspring. Neurobehav Toxicol Teratol 4(5):515–520

    CAS  PubMed  Google Scholar 

  90. Kwong WY et al (2000) Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development 127(19):4195–4202

    CAS  PubMed  Google Scholar 

  91. Levine S, Wiener S (1976) A critical analysis of data on malnutrition and behavioral deficits. Adv Pediatr 22:113–136

    CAS  PubMed  Google Scholar 

  92. Redila VA et al (2006) Hippocampal cell proliferation is reduced following prenatal ethanol exposure but can be rescued with voluntary exercise. Hippocampus 16(3):305–311

    CAS  PubMed  Google Scholar 

  93. Taylor AN et al (1988) Maternal alcohol consumption and stress responsiveness in offspring. Adv Exp Med Biol 245:311–317

    CAS  PubMed  Google Scholar 

  94. Yirmiya R et al (1998) Effects of prenatal alcohol and pair feeding on lipopolysaccharide-induced secretion of TNF-alpha and corticosterone. Alcohol 15(4):327–335

    CAS  PubMed  Google Scholar 

  95. Smotherman WP et al (1978) Orientation to rat pup cues - effects of maternal experiential history. Anim Behav 26(Feb):265–273

    Google Scholar 

  96. Ness JW, Franchina JJ (1990) Effects of prenatal alcohol exposure on rat pups ability to elicit retrieval behavior from dams. Dev Psychobiol 23(1):85–99

    CAS  PubMed  Google Scholar 

  97. Terkel J, Damassa DA, Sawyer CH (1979) Ultrasonic cries from infant rats stimulate prolactin-release in lactating mothers. Horm Behav 12(1):95–102

    CAS  PubMed  Google Scholar 

  98. Sewell GD (1970) Ultrasonic communication in rodents. Nature 227(5256):410

    CAS  PubMed  Google Scholar 

  99. Barron S, Gilbertson R (2005) Neonatal ethanol exposure but not neonatal cocaine selectively reduces specific isolation-induced vocalization waveforms in rats. Behav Genet 35:93–102

    PubMed  Google Scholar 

  100. Marino MD et al (2002) Ultrasonic vocalizations and maternal-infant interactions in a rat model of fetal alcohol syndrome. Dev Psychobiol 41(4):341–351

    PubMed  Google Scholar 

  101. Fernandez K et al (1983) Effects of prenatal alcohol on homing behavior, maternal responding and open-field activity in rats. Neurobehav Toxicol Teratol 5(3):351–356

    CAS  PubMed  Google Scholar 

  102. Barron S, Kelly SJ, Riley EP (1991) Neonatal alcohol exposure alters suckling behavior in neonatal rat pups. Pharmacol Biochem Behav 39(2):423–427

    CAS  PubMed  Google Scholar 

  103. Rockwood GA, Riley EP (1990) Nipple attachment behavior in rat pups exposed to alcohol in utero. Neurotoxicol Teratol 12(4):383–389

    CAS  PubMed  Google Scholar 

  104. Abel EL, Dintcheff BA (1978) Effects of prenatal alcohol exposure on growth and development in rats. J Pharmacol Exp Ther 207(3):916–921

    CAS  PubMed  Google Scholar 

  105. Osborne GL, Caul WF, Fernandez K (1980) Behavioral effects of prenatal ethanol exposure and differential early experience in rats. Pharmacol Biochem Behav 12(3):393–401

    CAS  PubMed  Google Scholar 

  106. Giberson PK, Weinberg J (1993) Fetal alcohol syndrome and functioning of the immune system. Alcohol Health Res World 16:29–38

    Google Scholar 

  107. Molet J et al (2014) Naturalistic rodent models of chronic early-life stress. Dev Psychobiol 56:1675

    PubMed  Google Scholar 

  108. Schneider ML et al (2002) The impact of prenatal stress, fetal alcohol exposure, or both on development: perspectives from a primate model. Psychoneuroendocrinology 27(1–2):285–298

    CAS  PubMed  Google Scholar 

  109. Schneider ML, Moore CF, Kraemer GW (2004) Moderate level alcohol during pregnancy, prenatal stress, or both and limbic-hypothalamic-pituitary-adrenocortical axis response to stress in rhesus monkeys. Child Dev 75(1):96–109

    PubMed  Google Scholar 

  110. Riley EP (1990) The long-term behavioral effects of prenatal alcohol exposure in rats. Alcohol Clin Exp Res 14(5):670–673

    CAS  PubMed  Google Scholar 

  111. Weinberg J et al (2008) Prenatal alcohol exposure: foetal programming, the hypothalamic-pituitary-adrenal axis and sex differences in outcome. J Neuroendocrinol 20(4):470–488

    CAS  PubMed  Google Scholar 

  112. Abel EL, Hannigan JH (1995) Maternal risk factors in fetal alcohol syndrome: provocative and permissive influences. Neurotoxicol Teratol 17(4):445–462

    CAS  PubMed  Google Scholar 

  113. Streissguth AP, Dehaene P (1993) Fetal alcohol syndrome in twins of alcoholic mothers - concordance of diagnosis and Iq. Am J Med Genet 47(6):857–861

    CAS  PubMed  Google Scholar 

  114. McClearn GE, Kakihana R (1981) Selective breeding for ethanol sensitivity: short-sleep and long-sleep mice. In: McClearn DE, Deitrich RA, Erwin VG (eds) Development of animal models as pharmacogenetic tools, vol 6, NIAAA research monograph. U.S. Government Printing Office, Washington, DC

    Google Scholar 

  115. Gilliam DM et al (1988) Ethanol teratogenesis in mice selected for differences in alcohol sensitivity. Alcohol 5(6):513–519

    CAS  PubMed  Google Scholar 

  116. Gilliam DM et al (1989) Ethanol teratogenesis in selectivity bred long-sleep and short-sleep mice: a comparison to inbred C57BL/6J mice. Alcohol Clin Exp Res 13(5):667–672

    CAS  PubMed  Google Scholar 

  117. Gilliam DM, Kotch LE (1996) Dose-related growth deficits in LS but not SS mice prenatally exposed to alcohol. Alcohol 13(1):47–51

    CAS  PubMed  Google Scholar 

  118. Downing C et al (2009) Ethanol teratogenesis in five inbred strains of mice. Alcohol Clin Exp Res 33(7):1238–1245

    PubMed Central  CAS  PubMed  Google Scholar 

  119. Chen Y et al (2011) Strain differences in developmental vulnerability to alcohol exposure via embryo culture in mice. Alcohol Clin Exp Res 35(7):1293–1304

    PubMed Central  PubMed  Google Scholar 

  120. Comeau WL, Winstanley CA, Weinberg J (2014) Prenatal alcohol exposure and adolescent stress - unmasking persistent attentional deficits in rats. Eur J Neurosci 40:3078

    PubMed Central  PubMed  Google Scholar 

  121. Gabriel KI et al (2006) Prenatal ethanol exposure alters sensitivity to the effects of corticotropin-releasing factor (CRF) on behavior in the elevated plus-maze. Psycho-neuroendocrinology 31(9):1046–1056

    CAS  Google Scholar 

  122. Hellemans KGC et al (2008) Prenatal alcohol exposure increases vulnerability to stress and anxiety-like disorders in adulthood. Ann N Y Acad Sci 1144(1):154–175

    CAS  PubMed  Google Scholar 

  123. Keiver K, Weinberg J (2004) Effect of duration of maternal alcohol consumption on calcium metabolism and bone in the fetal rat. Alcohol Clin Exp Res 28(3):456–467

    CAS  PubMed  Google Scholar 

  124. Kim CK et al (1999) Effects of prenatal exposure to alcohol on the release of adenocorticotropic hormone, corticosterone, and proinflammatory cytokines. Alcohol Clin Exp Res 23(1):52–59

    CAS  PubMed  Google Scholar 

  125. O’Neil R, Lan N, Innis S, Devlin A, Ellis L, Chan B, Weinberg J (2007) Metabolic effects of prenatal ethanol exposure and epigenetic reprogramming of the HPA axis. Alcohol Clin Exp Res 31:100A

    Google Scholar 

  126. Raineki C et al (2014) Neurocircuitry underlying stress and emotional regulation in animals prenatally exposed to alcohol and subjected to chronic mild stress in adulthood. Front Endocrinol (Lausanne) 5:5

    Google Scholar 

  127. Uban KA et al (2014) Amphetamine sensitization and cross-sensitization with acute restraint stress: impact of prenatal alcohol exposure in male and female rats. Psychopharmacology. doi:10.1007/s00213-014-3804-y

  128. Moore C (1992) The role of maternal stimulation in the development of sexual behavior and its neural basis. Ann N Y Acad Sci 662:160–177

    CAS  PubMed  Google Scholar 

  129. Moore CL, Chadwick-Dias AM (1986) Behavioral responses of infant rats to maternal licking: variations with age and sex. Dev Psychobiol 19(5):427–438

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The research in Dr. Weinberg’s laboratory is supported by grants from the National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism, NeuroDevNet (Canadian Network of Centres of Excellence), and Canadian Foundation on Fetal Alcohol Research. Student authors were supported by NSERC (TB, VL), IMPART (CIHR STIHR administered by BC Centre of Excellence for Women’s Health) (KU), and CFRI/NeuroDevNet Graduate Studentship (KAS).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joanne Weinberg Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Comeau, W., Bodnar, T., Uban, K., Lam, V., Stepien, K., Weinberg, J. (2015). Animal Models of Fetal Alcohol Spectrum Disorder. In: Yager, J. (eds) Animal Models of Neurodevelopmental Disorders. Neuromethods, vol 104. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2709-8_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2709-8_13

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2708-1

  • Online ISBN: 978-1-4939-2709-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics