title: Nucleus accumbens GABAergic inhibition generates intense eating and fear that resists environmental retuning and needs no local dopamine.
abstract: Intense fearful behavior and/or intense appetitive eating behavior can be generated by localized amino acid inhibitions along a rostrocaudal anatomical gradient within medial shell of nucleus accumbens of the rat. This can be produced by microinjections in medial shell of either the γ-aminobutyric acid (GABA)A agonist muscimol (mimicking intrinsic GABAergic inputs) or the AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) antagonist DNQX (6,7-dinitroquinoxaline-2,3-dione), disrupting corticolimbic glutamate inputs). At rostral sites in medial shell, each drug robustly stimulates appetitive eating and food intake, whereas at more caudal sites the same drugs instead produce increasingly fearful behaviors such as escape, distress vocalizations and defensive treading (an antipredator behavior rodents emit to snakes and scorpions). Previously we showed that intense motivated behaviors generated by glutamate blockade require local endogenous dopamine and can be modulated in valence by environmental ambience. Here we investigated whether GABAergic generation of intense appetitive and fearful motivations similarly depends on local dopamine signals, and whether the valence of motivations generated by GABAergic inhibition can also be retuned by changes in environmental ambience. We report that the answer to both questions is 'no'. Eating and fear generated by GABAergic inhibition of accumbens shell does not need endogenous dopamine. Also, the appetitive/fearful valence generated by GABAergic muscimol microinjections resists environmental retuning and is determined almost purely by rostrocaudal anatomical placement. These results suggest that nucleus accumbens GABAergic release of fear and eating are relatively independent of modulatory dopamine signals, and more anatomically pre-determined in valence balance than release of the same intense behaviors by glutamate disruptions.
authors.affiliation: Department of Psychology, University of Michigan, Ann Arbor, MI, USA. jrichard@gallo.ucsf.edu
authors.forename: Jocelyn M
authors.initials: JM
authors.lastname: Richard
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Plawecki
authors.forename: Kent C
authors.initials: KC
authors.lastname: Berridge
mesh_terms: D000818:Animals; D001070:Appetitive Behavior; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004435:Eating; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005239:Fear; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology*; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D004298:Dopamine
references.citation: J Neurosci. 1983 Jan;3(1):189-202
references.pmid: 6822855
references.citation: J Neurophysiol. 2002 Apr;87(4):2190-4
references.pmid: 11929936
references.citation: J Neurosci. 2003 Oct 15;23(28):9395-402
references.pmid: 14561867
references.citation: Brain Res Brain Res Rev. 1998 Dec;28(3):309-69
references.pmid: 9858756
references.citation: Philos Trans R Soc Lond B Biol Sci. 2004 Sep 29;359(1449):1395-411
references.pmid: 15347531
references.citation: Neuropsychopharmacology. 2000 Oct;23(4):455-67
references.pmid: 10989273
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10258-63
references.pmid: 17545307
references.citation: Schizophr Bull. 2009 May;35(3):549-62
references.pmid: 19325164
references.citation: J Neurosci. 2004 Feb 4;24(5):1040-9
references.pmid: 14762122
references.citation: Neuroscience. 1998 Apr;83(3):749-61
references.pmid: 9483559
references.citation: Korean J Physiol Pharmacol. 2009 Jun;13(3):209-14
references.pmid: 19885039
references.citation: Brain Struct Funct. 2008 Sep;213(1-2):17-27
references.pmid: 18256852
references.citation: J Comp Neurol. 1994 Jul 22;345(4):579-95
references.pmid: 7962701
references.citation: J Neurophysiol. 2007 Jul;98(1):423-32
references.pmid: 17522168
references.citation: Prog Neurobiol. 1994 Apr;42(6):719-61
references.pmid: 7938546
references.citation: Annu Rev Psychol. 2007;58:373-403
references.pmid: 17002554
references.citation: Brain Res. 1998 Jun 22;797(1):73-93
references.pmid: 9630528
references.citation: Brain Res. 1990 Apr 16;513(2):329-34
references.pmid: 2350704
references.citation: Clin Psychol Rev. 2010 Nov;30(7):839-48
references.pmid: 19939530
references.citation: J Comp Neurol. 1993 Apr 15;330(3):381-404
references.pmid: 8385679
references.citation: J Neurosci. 1997 Jun 1;17(11):4434-40
references.pmid: 9151760
references.citation: Neuropsychopharmacology. 2002 Feb;26(2):164-75
references.pmid: 11790512
references.citation: Neuroscience. 1987 Aug;22(2):425-39
references.pmid: 2823173
references.citation: Neurosci Biobehav Rev. 1997 Jul;21(4):519-23
references.pmid: 9195611
references.citation: Pflugers Arch. 2002 Mar;443(5-6):707-12
references.pmid: 11889567
references.citation: Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9576-80
references.pmid: 7692449
references.citation: J Neurosci. 2008 Mar 5;28(10):2633-41
references.pmid: 18322106
references.citation: Brain Res. 1999 Mar 20;822(1-2):88-106
references.pmid: 10082887
references.citation: J Comp Neurol. 1987 Apr 15;258(3):317-38
references.pmid: 2884240
references.citation: J Neurosci. 2011 Sep 7;31(36):12866-79
references.pmid: 21900565
references.citation: J Neurosci Methods. 1980 Dec;3(2):129-49
references.pmid: 6110810
references.citation: Pharmacol Biochem Behav. 1981 Oct;15(4):619-26
references.pmid: 6117086
references.citation: J Neurosci. 2010 Mar 31;30(13):4746-56
references.pmid: 20357125
references.citation: Brain Res. 1995 Jun 5;682(1-2):215-21
references.pmid: 7552315
references.citation: J Neurophysiol. 2008 Mar;99(3):1267-73
references.pmid: 18199816
references.citation: Cogn Affect Behav Neurosci. 2007 Dec;7(4):391-5
references.pmid: 18189012
references.citation: Nat Neurosci. 2008 Dec;11(12):1376-7
references.pmid: 18978779
references.citation: Pharmacol Biochem Behav. 1997 Nov;58(3):801-11
references.pmid: 9329075
references.citation: J Neurosci. 2001 May 1;21(9):3261-70
references.pmid: 11312311
references.citation: Eur J Neurosci. 2003 May;17(10):2187-200
references.pmid: 12786986
references.citation: J Comp Neurol. 1990 Dec 15;302(3):437-46
references.pmid: 1702109
references.citation: J Neurosci. 2008 Jul 9;28(28):7184-92
references.pmid: 18614688
references.citation: Prog Brain Res. 1993;99:3-24
references.pmid: 7906426
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15235-9
references.pmid: 20696892
references.citation: J Comp Neurol. 1993 Dec 8;338(2):255-78
references.pmid: 8308171
references.citation: Prog Brain Res. 2007;160:21-41
references.pmid: 17499107
references.citation: J Comp Neurol. 1979 Mar 1;184(1):43-62
references.pmid: 762282
references.citation: J Comp Neurol. 2013 Jan 1;521(1):50-68
references.pmid: 22628122
references.citation: Neuroscience. 1991;41(1):89-125
references.pmid: 2057066
references.citation: Neuropsychopharmacology. 2008 Feb;33(3):473-9
references.pmid: 17473838
references.citation: J Neurosci. 1995 Oct;15(10):6779-88
references.pmid: 7472436
references.citation: J Comp Neurol. 1992 Jun 8;320(2):145-60
references.pmid: 1377716
references.citation: Neuroscience. 1997 Feb;76(4):1105-12
references.pmid: 9027870
references.citation: Psychol Rev. 2003 Jan;110(1):145-72
references.pmid: 12529060
references.citation: Nat Neurosci. 2008 Apr;11(4):423-5
references.pmid: 18344996
references.citation: J Neurosci Methods. 1989 Sep;29(3):261-5
references.pmid: 2507830
references.citation: Ann N Y Acad Sci. 1999 Jun 29;877:71-90
references.pmid: 10415644
references.citation: J Neurosci. 2001 Sep 15;21(18):RC165
references.pmid: 11549754
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2007 Nov 15;31(8):1556-71
references.pmid: 17884274
references.citation: J Neurosci. 2004 Sep 8;24(36):7916-22
references.pmid: 15356204
references.citation: Biol Psychiatry. 2008 Mar 15;63(6):577-86
references.pmid: 17888411
references.citation: J Comp Neurol. 1993 Jan 8;327(2):220-32
references.pmid: 8425943
references.citation: Neuropsychopharmacology. 2006 Oct;31(10):2091-120
references.pmid: 16541087
references.citation: J Neurosci. 2010 May 19;30(20):7105-10
references.pmid: 20484653
references.citation: J Neurosci. 2002 Aug 15;22(16):7308-20
references.pmid: 12177226
references.citation: PLoS One. 2010 Jun 18;5(6):e11223
references.pmid: 20585461