title: Rodent models for compulsive alcohol intake.
abstract: Continued seeking and drinking of alcohol despite adverse legal, health, economic, and societal consequences is a central hallmark of human alcohol use disorders. This compulsive drive for alcohol, defined by resistance to adverse and deleterious consequences, represents a major challenge when attempting to treat alcoholism clinically. Thus, there has long been interest in developing pre-clinical rodent models for the compulsive drug use that characterizes drug addiction. Here, we review recent studies that have attempted to model compulsive aspects of alcohol and cocaine intake in rodents, and consider technical and conceptual issues that need to be addressed when trying to recapitulate compulsive aspects of human addiction. Aversion-resistant alcohol intake has been examined by pairing intake or seeking with the bitter tastant quinine or with footshock, and exciting recent work has used these models to identify neuroadaptations in the amygdala, cortex, and striatal regions that promote compulsive intake. Thus, rodent models do seem to reflect important aspects of compulsive drives that sustain human addiction, and will likely provide critical insights into the molecular and circuit underpinnings of aversion-resistant intake as well as novel therapeutic interventions for compulsive aspects of addiction.
authors.affiliation: Department of Neurology, Ernest Gallo Clinic and Research Center, University of California, 675 Nelson Rising Lane, Room 490D, San Francisco, CA 94158, USA. Electronic address: Frederic.Hopf@ucsf.edu.
authors.forename: F Woodward
authors.initials: FW
authors.lastname: Hopf
authors.affiliation: Department of Animals in Science and Society, Division of Behavioural Neuroscience, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Heidi M B
authors.initials: HM
authors.lastname: Lesscher
mesh_terms: D000428:Alcohol Drinking / Q000523:psychology*; D000679:Amygdala / Q000502:physiology; D000818:Animals; D003192:Compulsive Behavior; D003342:Corpus Striatum / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D023421:Models, Animal; D011803:Quinine / Q000494:pharmacology; D051381:Rats; D013649:Taste
chemical_list: D011803:Quinine
keywords: Accumbens; Adaptation; Addiction; Alcohol; Aversion; Central amygdala; Circuit; Compulsion; Cortex; Glutamate receptor; Intracellular signaling; Ion channel; Punishment; Striatum
references.citation: J Neurosci. 2012 May 30;32(22):7563-71
references.pmid: 22649234
references.citation: Alcohol Alcohol. 2004 May-Jun;39(3):183-9
references.pmid: 15082454
references.citation: Eur J Neurosci. 2012 Mar;35(5):775-83
references.pmid: 22304754
references.citation: Addict Biol. 2006 Mar;11(1):2-38
references.pmid: 16759333
references.citation: Pharmacol Biochem Behav. 1991 Feb;38(2):389-99
references.pmid: 2057508
references.citation: Physiol Rev. 2009 Apr;89(2):649-705
references.pmid: 19342616
references.citation: J Neurosci. 1995 Aug;15(8):5439-47
references.pmid: 7643193
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12518-23
references.pmid: 17626178
references.citation: Addiction. 2000 Aug;95(8 Suppl 2):145-153
references.pmid: 11002909
references.citation: Int J Neuropsychopharmacol. 2011 Sep;14(8):1099-110
references.pmid: 21205431
references.citation: Nature. 1997 Jul 24;388(6640):377-80
references.pmid: 9237754
references.citation: Addict Biol. 2009 Sep;14(4):384-96
references.pmid: 19740366
references.citation: Psychopharmacology (Berl). 2007 Sep;194(1):117-25
references.pmid: 17558499
references.citation: Alcohol Clin Exp Res. 2013 Jan;37 Suppl 1:E322-8
references.pmid: 22757984
references.citation: Neuron. 2004 Nov 18;44(4):729-40
references.pmid: 15541319
references.citation: Philos Trans R Soc Lond B Biol Sci. 2008 Oct 12;363(1507):3125-35
references.pmid: 18640910
references.citation: J Neurosci. 2010 Nov 17;30(46):15457-63
references.pmid: 21084602
references.citation: Nat Neurosci. 2013 Aug;16(8):1094-100
references.pmid: 23817545
references.citation: Biol Psychiatry. 2009 Jul 15;66(2):185-90
references.pmid: 19249750
references.citation: Addict Biol. 2012 Sep;17(5):920-33
references.pmid: 22741603
references.citation: Pharmacol Biochem Behav. 2008 Sep;90(3):470-4
references.pmid: 18499241
references.citation: J Cogn Neurosci. 2008 Jun;20(6):1063-78
references.pmid: 18211237
references.citation: Genes Brain Behav. 2009 Jul;8(5):493-9
references.pmid: 19243450
references.citation: PLoS One. 2009 Jun 10;4(6):e5865
references.pmid: 19517024
references.citation: Eur J Pharmacol. 1996 Jun 3;305(1-3):39-44
references.pmid: 8813529
references.citation: Pharmacogenet Genomics. 2009 Sep;19(9):719-29
references.pmid: 19680168
references.citation: Neurosci Biobehav Rev. 2010 Nov;35(2):232-47
references.pmid: 20493211
references.citation: Psychopharmacologia. 1973;29(3):203-10
references.pmid: 4702273
references.citation: Eur Addict Res. 2006;12(4):210-21
references.pmid: 16968996
references.citation: Psychopharmacology (Berl). 2005 Oct;181(4):688-96
references.pmid: 16001125
references.citation: Neurosci Biobehav Rev. 2010 Nov;35(2):212-9
references.pmid: 20097224
references.citation: J Neurosci. 2004 Nov 10;24(45):10159-66
references.pmid: 15537886
references.citation: Addict Biol. 2009 Jan;14(1):43-64
references.pmid: 18855803
references.citation: Pharmacol Biochem Behav. 2012 Aug;102(2):233-40
references.pmid: 22579911
references.citation: Neuron. 2005 Oct 20;48(2):175-87
references.pmid: 16242399
references.citation: Nat Rev Neurosci. 2004 Nov;5(11):844-52
references.pmid: 15496862
references.citation: Addict Biol. 2011 Oct;16(4):600-14
references.pmid: 21762292
references.citation: PLoS One. 2012;7(5):e37999
references.pmid: 22629472
references.citation: Trends Neurosci. 2003 Apr;26(4):184-92
references.pmid: 12689769
references.citation: Neuron. 2008 Feb 7;57(3):432-41
references.pmid: 18255035
references.citation: Nat Neurosci. 2012 Jun;15(6):920-5
references.pmid: 22544311
references.citation: Neuroscience. 2012 Jun 1;211:107-25
references.pmid: 21864653
references.citation: J Neurosci. 2013 Feb 13;33(7):2794-806
references.pmid: 23407939
references.citation: Neuropsychopharmacology. 2013 Jan;38(1):198-211
references.pmid: 22968819
references.citation: Physiol Behav. 2005 Jan 31;84(1):53-63
references.pmid: 15642607
references.citation: Behav Neurosci. 2011 Dec;125(6):930-42
references.pmid: 21988520
references.citation: Nature. 2010 Nov 11;468(7321):277-82
references.pmid: 21068837
references.citation: Brain Struct Funct. 2010 Jun;214(5-6):435-50
references.pmid: 20512364
references.citation: Nature. 2013 Apr 18;496(7445):359-62
references.pmid: 23552889
references.citation: Neurosci Biobehav Rev. 2006;30(2):215-38
references.pmid: 16099045
references.citation: Proc Natl Acad Sci U S A. 1988 Jul;85(14):5274-8
references.pmid: 2899326
references.citation: Eur J Pharmacol. 1996 Jun 3;305(1-3):45-50
references.pmid: 8813530
references.citation: Ann N Y Acad Sci. 1999 Jun 29;877:412-38
references.pmid: 10415662
references.citation: Biol Psychiatry. 2008 Aug 1;64(3):192-202
references.pmid: 18374900
references.citation: Psychol Rev. 1990 Apr;97(2):147-68
references.pmid: 2186423
references.citation: Neuropsychopharmacology. 2010 Jan;35(1):217-38
references.pmid: 19710631
references.citation: Brain. 2010 May;133(Pt 5):1484-93
references.pmid: 20395264
references.citation: J Neurosci. 2009 Apr 15;29(15):4846-57
references.pmid: 19369553
references.citation: Alcohol Clin Exp Res. 2008 Oct;32(10):1816-23
references.pmid: 18671810
references.citation: Alcohol Clin Exp Res. 2010 Sep 1;34(9):1565-73
references.pmid: 20586757
references.citation: Addict Biol. 2006 Sep;11(3-4):270-88
references.pmid: 16961759
references.citation: Nat Neurosci. 2009 Feb;12(2):200-9
references.pmid: 19151710
references.citation: Lancet. 2007 Jun 16;369(9578):2001-2009
references.pmid: 17574092
references.citation: Neuropsychopharmacology. 2013 Sep;38(10):2048-56
references.pmid: 23624743
references.citation: Neuropsychopharmacology. 2012 Oct;37(11):2505-14
references.pmid: 22763621
references.citation: Psychopharmacology (Berl). 2012 Feb;219(3):875-83
references.pmid: 21792542
references.citation: Pharmacol Biochem Behav. 2008 Sep;90(3):475-80
references.pmid: 18501411
references.citation: Brain Res. 2002 Sep 6;948(1-2):186-91
references.pmid: 12383974
references.citation: J Neurosci. 2006 Nov 1;26(44):11324-32
references.pmid: 17079660
references.citation: Alcohol Alcohol. 1999 Mar-Apr;34(2):231-43
references.pmid: 10344783
references.citation: J Neurosci. 2008 Mar 5;28(10):2589-600
references.pmid: 18322102
references.citation: Addiction. 2000 Aug;95 Suppl 2:S211-7
references.pmid: 11002915
references.citation: Addict Biol. 2013 May;18(3):496-507
references.pmid: 22862671
references.citation: J Neurosci. 2013 Aug 28;33(35):13989-4000
references.pmid: 23986236
references.citation: Science. 2004 Aug 13;305(5686):1017-9
references.pmid: 15310907
references.citation: Neuropharmacology. 2004;47 Suppl 1:190-201
references.pmid: 15464137
references.citation: Alcohol Clin Exp Res. 2011 Apr;35(4):643-51
references.pmid: 21223301
references.citation: J Neural Transm (Vienna). 2006 Sep;113(9):1305-21
references.pmid: 16465467
references.citation: Q J Exp Psychol B. 2002 Oct;55(4):331-48
references.pmid: 12350285
references.citation: Eur J Neurosci. 2001 May;13(10):1984-92
references.pmid: 11403692
references.citation: Alcohol Clin Exp Res. 2010 Dec;34(12):2147-54
references.pmid: 20860609
references.citation: Alcohol Clin Exp Res. 2002 Jun;26(6):796-803
references.pmid: 12068247
references.citation: J Neurosci. 2012 Mar 28;32(13):4645-50
references.pmid: 22457510
references.citation: Pharmacol Ther. 2011 Feb;129(2):149-71
references.pmid: 20951730
references.citation: Mol Psychiatry. 2013 Jun;18(6):729-37
references.pmid: 22584869
references.citation: Neuropsychopharmacology. 2011 Feb;36(3):569-79
references.pmid: 20980989
references.citation: Alcohol Res Health. 1999;23(2):151-60
references.pmid: 10890810
references.citation: Neuropsychopharmacology. 2000 Jun;22(6):581-94
references.pmid: 10788758
references.citation: Cold Spring Harb Perspect Med. 2012 Nov 01;2(11):
references.pmid: 23125204
references.citation: Addiction. 2010 Oct;105(10):1741-9
references.pmid: 20670348
references.citation: Am J Psychiatry. 2001 Jul;158(7):1075-83
references.pmid: 11431229
references.citation: Nat Neurosci. 2005 Nov;8(11):1481-9
references.pmid: 16251991
references.citation: Neuropharmacology. 2009;56 Suppl 1:18-31
references.pmid: 18725236
references.citation: Science. 2004 Aug 13;305(5686):1014-7
references.pmid: 15310906
references.citation: Biol Psychiatry. 2013 Feb 1;73(3):256-62
references.pmid: 22883434
references.citation: Neurobiol Dis. 2009 Oct;36(1):1-10
references.pmid: 19501165
references.citation: Am J Psychiatry. 1999 Jan;156(1):11-8
references.pmid: 9892292
references.citation: Brain. 2007 May;130(Pt 5):1330-7
references.pmid: 17405766
references.citation: ILAR J. 2011;52(3):239-50
references.pmid: 23382142
references.citation: J Intensive Care Med. 2003 May-Jun;18(3):150-5
references.pmid: 14984634
references.citation: Ann N Y Acad Sci. 2011 Jan;1216:24-40
references.pmid: 21272009
references.citation: Rev Neurosci. 2012;23(5-6):731-45
references.pmid: 23079511
references.citation: Nat Neurosci. 2010 May;13(5):635-41
references.pmid: 20348917
references.citation: Addict Biol. 2010 Apr;15(2):169-84
references.pmid: 20148778
references.citation: Alcohol Clin Exp Res. 2013 Jul;37(7):1100-10
references.pmid: 23398292
references.citation: Best Pract Res Clin Gastroenterol. 2003 Aug;17(4):575-92
references.pmid: 12828956
references.citation: Am J Psychiatry. 2008 Sep;165(9):1179-84
references.pmid: 18593776
references.citation: Alcohol Clin Exp Res. 2010 Jul;34(7):1219-25
references.pmid: 20477770
references.citation: Biol Psychiatry. 2012 Sep 1;72(5):389-95
references.pmid: 22440617
references.citation: J Neural Transm (Vienna). 2000;107(6):649-68
references.pmid: 10943906
references.citation: Alcohol Clin Exp Res. 2003 Feb;27(2):232-43
references.pmid: 12605072
references.citation: Curr Opin Neurobiol. 2013 Aug;23(4):564-72
references.pmid: 23452942
references.citation: PLoS One. 2012;7(8):e42886
references.pmid: 22870342