title: Is the rodent maternal separation model a valid and effective model for studies on the early-life impact on ethanol consumption?
abstract: BACKGROUND
  Early-life events can cause long-term neurobiological and behavioural changes with a resultant effect upon reward and addiction processes that enhance risk to develop alcohol use disorders. Maternal separation (MS) is used to study the mediating mechanisms of early-life influences in rodents. In MS studies, the pups are exposed to maternal absence during the first postnatal weeks. The outcome of MS experiments exhibits considerable variation and questions have been raised about the validity of MS models.
  
  
  OBJECTIVE
  This short review aims to provide information about experimental conditions that are important to consider when assessing the impact of early-life environment on voluntary ethanol consumption.
  
  
  RESULTS
  The results from currently used MS protocols are not uniform. However, studies consistently show that longer separations of intact litters predispose for higher ethanol consumption and/or preference in adult male rats as compared to shorter periods of MS. Studies using individual pup MS paradigms, other controls, low ethanol concentrations, adult females or examining adolescent consumption reported no differences or inconsistent results.
  
  
  CONCLUSIONS
  There is no "a rodent MS model", there are several models and they generate different results. The compiled literature shows that MS is a model of choice for analysis of early-life effects on voluntary ethanol consumption but there are examples of MS paradigms that are not suitable. These studies emphasize the importance to carefully designed MS experiments to supply the optimal conditions to definitely test the research hypothesis and to be particulate in the interpretation of the outcome.
authors: Department of Pharmaceutical Biosciences, Neuropharmacology Addiction & Behaviour, Uppsala University, Box 591, 751 24, Uppsala, Sweden, ingrid.nylander@farmbio.uu.se.
authors: Ingrid
authors: I
authors: Nylander
authors: Erika
authors: E
authors: Roman
mesh_terms: D000367:Age Factors; D000428:Alcohol Drinking / Q000453:epidemiology* / Q000523:psychology; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008426:Maternal Deprivation; D051379:Mice; D051381:Rats; D012201:Reward; D013315:Stress, Psychological / Q000523:psychology*
chemical_list: D000431:Ethanol
references: Science. 1940 May 24;91(2369):507-8
references: 17847448
references: Rev Neurosci. 2000;11(4):383-408
references: 11065281
references: Psychopharmacology (Berl). 2005 Aug;181(1):8-15
references: 15830234
references: J Clin Psychiatry. 2004;65 Suppl 1:18-28
references: 14728093
references: Pharmacol Biochem Behav. 1994 Dec;49(4):961-7
references: 7886114
references: Alcohol Clin Exp Res. 2006 Dec;30(12):2008-16
references: 17117966
references: Neurosci Biobehav Rev. 2010 May;34(6):821-34
references: 19751762
references: J Psychiatr Ment Health Nurs. 2009 Mar;16(2):137-45
references: 19281544
references: Dev Psychobiol. 2004 Sep;45(2):59-71
references: 15340975
references: Horm Behav. 2006 Dec;50(5):667-80
references: 16890940
references: Front Neuroendocrinol. 2008 Jun;29(3):344-57
references: 18358518
references: Neuropharmacology. 2012 Apr;62(5-6):1944-53
references: 22245561
references: Brain Res. 2009 Dec 11;1305 Suppl:S37-49
references: 19728999
references: Brain Res. 2011 Aug 8;1405:57-68
references: 21741625
references: Neurosci Biobehav Rev. 2003 Jan-Mar;27(1-2):73-82
references: 12732224
references: Alcohol Clin Exp Res. 2005 Oct;29(10):1796-808
references: 16269909
references: Behav Brain Res. 2007 Dec 3;184(2):109-16
references: 17675171
references: Addict Biol. 2008 Mar;13(1):1-14
references: 17910738
references: Neurosci Biobehav Rev. 2009 Apr;33(4):516-24
references: 18938197
references: Alcohol. 2004 May;33(1):31-9
references: 15353171
references: Brain Res. 2006 Jul 12;1099(1):101-8
references: 16784730
references: Annu Rev Neurosci. 2001;24:1161-92
references: 11520931
references: Pharmacol Biochem Behav. 2012 Jan;100(3):630-8
references: 22108648
references: Neurosci Biobehav Rev. 2000 Jun;24(4):417-63
references: 10817843
references: Ann N Y Acad Sci. 2008 Oct;1141:105-30
references: 18991954
references: Alcohol Clin Exp Res. 2003 May;27(5):812-7
references: 12766626
references: Psychopharmacologia. 1973;29(3):203-10
references: 4702273
references: Eur J Neurosci. 2004 Apr;19(7):1863-74
references: 15078560
references: Drug Alcohol Depend. 2008 Jan 11;93(1-2):51-62
references: 18029114
references: Addiction. 2007 Mar;102(3):389-98
references: 17298646
references: Pharmacol Biochem Behav. 2007 Feb;86(2):234-45
references: 16930684
references: Addict Biol. 2006 Sep;11(3-4):289-309
references: 16961760
references: Neuroscience. 2006 Jun 19;140(1):355-65
references: 16530973
references: Science. 2002 Aug 2;297(5582):851-4
references: 12161658
references: Alcohol Clin Exp Res. 1998 Jun;22(4):830-6
references: 9660308
references: Anim Behav. 1970 Feb;18(1):144-50
references: 5530113
references: J Neurobiol. 2003 Jan;54(1):283-311
references: 12486710
references: Horm Behav. 2006 Dec;50(5):736-47
references: 16876800
references: Biochem Pharmacol. 2007 Feb 1;73(3):321-30
references: 16962564
references: Behav Brain Res. 2005 Jun 20;161(2):204-12
references: 15922046
references: Neuroscience. 2007 Mar 16;145(2):568-78
references: 17275195
references: Stress. 2005 Sep;8(3):157-74
references: 16323264
references: Alcohol Clin Exp Res. 2007 Jul;31(7):1159-68
references: 17511750
references: Trends Pharmacol Sci. 2010 Oct;31(10):463-9
references: 20684996
references: Neurosci Biobehav Rev. 2005;29(8):1335-46
references: 16095695
references: Front Psychiatry. 2011 Jul 28;2:48
references: 21847382
references: Physiol Behav. 2005 Jan 31;84(1):53-63
references: 15642607
references: Curr Top Behav Neurosci. 2013;13:355-77
references: 22371267
references: Drug Alcohol Depend. 2010 May 1;108(3):172-82
references: 20074870
references: Physiol Behav. 2012 Apr 12;106(1):29-39
references: 21888923
references: Neurosci Biobehav Rev. 1997 May;21(3):309-26
references: 9168267
references: Int J Dev Neurosci. 1998 Jun-Jul;16(3-4):261-70
references: 9785122
references: Neurosci Biobehav Rev. 2002 Dec;26(8):907-23
references: 12667496
references: Pharmacol Biochem Behav. 2012 Nov;103(1):119-55
references: 22841890
references: Prog Brain Res. 2000;122:81-103
references: 10737052
references: Psychopharmacology (Berl). 2011 Nov;218(1):131-56
references: 21850445
references: Alcohol Clin Exp Res. 2008 Oct;32(10):1816-23
references: 18671810
references: J Neurosci. 2005 May 4;25(18):4453-62
references: 15872092
references: Int J Dev Neurosci. 1998 Jun-Jul;16(3-4):149-64
references: 9785112
references: Pharmacol Biochem Behav. 2005 Jul;81(3):506-16
references: 15927243
references: Curr Top Behav Neurosci. 2013;13:223-49
references: 21706389
references: Psychoneuroendocrinology. 2002 Jan-Feb;27(1-2):127-38
references: 11750774
references: Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7261-5
references: 1871131
references: Pharmacol Ther. 2008 Nov;120(2):102-28
references: 18789966
references: Dev Neurosci. 2012;34(2-3):210-7
references: 22776911
references: Alcohol Clin Exp Res. 2004 Mar;28(3):441-7
references: 15084902
references: Brain Res. 1991 Mar 1;542(2):286-92
references: 1851458
references: Science. 1957 Aug 30;126(3270):405
references: 13467220
references: Br J Pharmacol. 2008 May;154(2):275-87
references: 18362899
references: Neuroscience. 2012 Oct 25;223:296-304
references: 22890080
references: Neuropsychopharmacology. 2003 Aug;28(8):1546-52
references: 12813472
references: Front Mol Neurosci. 2012 Jul 05;5:77
references: 22783165
references: Psychopharmacology (Berl). 2012 Nov;224(1):33-56
references: 22955569
references: Synapse. 1999 Apr;32(1):37-43
references: 10188636
references: Alcohol Clin Exp Res. 2013 Jun;37(6):984-92
references: 23278300
references: Dev Psychobiol. 1992 Apr;25(3):213-26
references: 1618372
references: Science. 1959 Jan 2;129(3340):42-3
references: 13615320
references: Science. 1954 Feb 26;119(3087):285-6
references: 13135523
references: Psychopharmacology (Berl). 2004 Nov;176(3-4):248-55
references: 15173929
references: Neurosci Biobehav Rev. 2003 Jan-Mar;27(1-2):33-44
references: 12732221
references: Science. 1999 Jun 4;284(5420):1670-2
references: 10356397
references: Neuroscience. 2003;121(3):787-99
references: 14568037
references: Horm Behav. 2011 Jul;60(2):165-76
references: 21570400
references: Psychopharmacology (Berl). 1996 Jul;126(1):75-84
references: 8853220
references: Peptides. 2012 Jul;36(1):1-8
references: 22564490
references: Alcohol Clin Exp Res. 2011 Mar;35(3):506-15
references: 21143247
references: Psychoneuroendocrinology. 2002 Jan-Feb;27(1-2):155-70
references: 11750776
references: Addict Biol. 2006 Mar;11(1):2-38
references: 16759333
references: Alcohol Clin Exp Res. 2005 Apr;29(4):591-601
references: 15834224
references: Psychopharmacology (Berl). 2001 Dec;158(4):366-73
references: 11797057
references: Neurosci Biobehav Rev. 2005 Apr;29(2):271-81
references: 15811498
references: Alcohol Clin Exp Res. 2010 Jun;34(6):976-87
references: 20374217
references: Psychopharmacology (Berl). 2011 Mar;214(1):141-54
references: 21165737
references: Pharmacol Biochem Behav. 2011 Oct;99(4):626-33
references: 21689677
references: Alcohol Clin Exp Res. 2009 Apr;33(4):722-8
references: 19183130
references: Behav Brain Res. 2005 Jan 30;156(2):297-310
references: 15582116
references: Neuropeptides. 2005 Dec;39(6):587-94
references: 16266747
references: Alcohol Clin Exp Res. 2003 Jan;27(1):31-7
references: 12544002
references: Physiol Behav. 2012 Jun 6;106(3):325-31
references: 22245775
references: Neurosci Biobehav Rev. 2003 Jan-Mar;27(1-2):57-71
references: 12732223
references: Addict Biol. 2011 Apr;16(2):347-55
references: 20731636
references: Pharmacol Biochem Behav. 2002 Aug;73(1):123-9
references: 12076731
references: Ann N Y Acad Sci. 2011 Jan;1216:24-40
references: 21272009
references: Neuropeptides. 2010 Oct;44(5):391-8
references: 20591479
references: Neuropeptides. 2003 Jun;37(3):149-56
references: 12860112
references: Synapse. 2001 Apr;40(1):1-10
references: 11170216
references: Psychopharmacology (Berl). 2008 Dec;201(3):459-68
references: 18766329
references: Neuropeptides. 2008 Apr;42(2):177-91
references: 18082882
references: Physiol Behav. 1987;40(3):401-6
references: 3659157
references: Psychopharmacology (Berl). 2011 Mar;214(1):131-40
references: 21086114
references: Child Adolesc Psychiatr Clin N Am. 2007 Apr;16(2):271-83, vii
references: 17349508
references: Psychoneuroendocrinology. 2009 Dec;34 Suppl 1:S217-26
references: 19553026
references: Trends Genet. 2009 Jan;25(1):49-55
references: 19010566
references: Physiol Behav. 1972 Nov-Dec;9(5):737-40
references: 4570173
references: Int Rev Neurobiol. 2003;54:107-43
references: 12785286
references: Dev Psychobiol. 2004 Nov;45(3):140-52
references: 15505796
references: Alcohol Clin Exp Res. 1996 Sep;20(6):1043-9
references: 8892526
references: Int J Neuropsychopharmacol. 2007 Oct;10(5):595-607
references: 17134528
references: Alcohol. 2011 Sep;45(6):607-14
references: 21168301