title: Involvement of Dopamine D1/D5 and D2 Receptors in Context-Dependent Extinction Learning and Memory Reinstatement.
abstract: Dopamine contributes to the regulation of higher order information processing and executive control. It is important for memory consolidation processes, and for the adaptation of learned responses based on experience. In line with this, under aversive learning conditions, application of dopamine receptor antagonists prior to extinction result in enhanced memory reinstatement. Here, we investigated the contribution of the dopaminergic system to extinction and memory reinstatement (renewal) of an appetitive spatial learning task in rodents. Rats were trained for 3 days in a T-maze (context "A") to associate a goal arm with a food reward, despite low reward probability (acquisition phase). On day 4, extinction learning (unrewarded) occurred, that was reinforced by a context change ("B"). On day 5, re-exposure to the (unrewarded) "A" context took place (renewal of context "A", followed by extinction of context "A"). In control animals, significant extinction occurred on day 4, that was followed by an initial memory reinstatement (renewal) on day 5, that was, in turn, succeeded by extinction of renewal. Intracerebral treatment with a D1/D5-receptor antagonist prior to the extinction trials, elicited a potent enhancement of extinction in context "B". By contrast, a D1/D5-agonist impaired renewal in context "A". Extinction in the "A" context on day 5 was unaffected by the D1/D5-ligands. Treatment with a D2-receptor antagonist prior to extinction had no overall effect on extinction in context "B" or renewal in context "A", although extinction of the renewal effect was impaired on day 5, compared to controls. Taken together, these data suggest that dopamine acting on the D1/D5-receptor modulates both acquisition and consolidation of context-dependent extinction. By contrast, the D2-receptor may contribute to context-independent aspects of this kind of extinction learning.
authors.affiliation: Medical Faculty, Department of Neurophysiology, Ruhr University BochumBochum, Germany; International Graduate School for Neuroscience, Ruhr University BochumBochum, Germany.
authors.forename: Marion Agnès Emma
authors.initials: MA
authors.lastname: André
authors.affiliation: Medical Faculty, Department of Neurophysiology, Ruhr University BochumBochum, Germany; International Graduate School for Neuroscience, Ruhr University BochumBochum, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Manahan-Vaughan
keywords: behavior; dopamine; extinction learning; hippocampus; rodent; spatial learning
references.citation: Cereb Cortex. 2012 Jul;22(7):1614-21
references.pmid: 21917740
references.citation: Hippocampus. 2014 Mar;24(3):270-9
references.pmid: 24132946
references.citation: Behav Neurosci. 1991 Aug;105(4):499-509
references.pmid: 1930720
references.citation: J Neurosci. 2006 Jul 19;26(29):7723-9
references.pmid: 16855100
references.citation: Brain Res Rev. 2007 Nov;56(1):27-78
references.pmid: 17574681
references.citation: Proc Natl Acad Sci U S A. 2004 May 25;101(21):8192-7
references.pmid: 15150407
references.citation: Behav Neurosci. 1998 Aug;112(4):952-65
references.pmid: 9733202
references.citation: Neurobiol Learn Mem. 2008 Jul;90(1):217-22
references.pmid: 18442937
references.citation: Behav Brain Res. 2015 Feb 1;278:527-34
references.pmid: 25446753
references.citation: Behav Res Ther. 2008 Jan;46(1):5-27
references.pmid: 18005936
references.citation: J Neurosci. 2001 Mar 1;21(5):1720-6
references.pmid: 11222661
references.citation: Psychopharmacology (Berl). 2001 Jan 1;153(2):170-9
references.pmid: 11205416
references.citation: J Comp Neurol. 2002 Dec 2;454(1):15-33
references.pmid: 12410615
references.citation: Prog Neurobiol. 2004 Dec;74(5):301-20
references.pmid: 15582224
references.citation: J Neurosci. 2014 Sep 24;34(39):13151-62
references.pmid: 25253860
references.citation: Learn Mem. 2012 Jan 17;19(2):67-72
references.pmid: 22251891
references.citation: Learn Mem. 2005 Jul-Aug;12(4):399-406
references.pmid: 16077018
references.citation: Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):E2428-36
references.pmid: 23754384
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4894-9
references.pmid: 19261850
references.citation: J Neurochem. 1989 May;52(5):1655-8
references.pmid: 2709017
references.citation: Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2446-50
references.pmid: 7708662
references.citation: Brain Res. 1995 Mar 27;675(1-2):325-8
references.pmid: 7796146
references.citation: Cereb Cortex. 2003 Feb;13(2):123-35
references.pmid: 12507943
references.citation: Eur J Pharmacol. 1997 Oct 8;336(2-3):107-12
references.pmid: 9384221
references.citation: J Neurosci. 2008 Jul 9;28(28):7184-92
references.pmid: 18614688
references.citation: Learn Mem. 2005 May-Jun;12(3):270-6
references.pmid: 15930505
references.citation: Neuropharmacology. 2013 Apr;67:104-14
references.pmid: 23164618
references.citation: Science. 2006 Aug 25;313(5790):1093-7
references.pmid: 16931756
references.citation: Cereb Cortex. 2013 May;23(5):1118-25
references.pmid: 22510536
references.citation: Behav Brain Res. 2014 Sep 1;271:212-7
references.pmid: 24959860
references.citation: Hippocampus. 2014 Dec;24(12):1615-22
references.pmid: 25112177
references.citation: Biol Psychiatry. 2010 Dec 1;68(11):1055-60
references.pmid: 20926066
references.citation: Neurobiol Learn Mem. 2014 Feb;108:65-77
references.pmid: 24269353
references.citation: J Neural Transm Gen Sect. 1993;93(1):11-25
references.pmid: 8373553
references.citation: PLoS Biol. 2014 Mar 18;12(3):e1001811
references.pmid: 24642480
references.citation: Trends Neurosci. 2005 Nov;28(11):574-82
references.pmid: 16165227
references.citation: Annu Rev Psychol. 2006;57:87-115
references.pmid: 16318590
references.citation: J Neurosci. 1997 May 1;17(9):3303-11
references.pmid: 9096163
references.citation: Learn Mem. 2000 May-Jun;7(3):187-91
references.pmid: 10837508
references.citation: Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8739-44
references.pmid: 10411945
references.citation: Front Behav Neurosci. 2015 May 27;9:125
references.pmid: 26074793
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12764-9
references.pmid: 22802650
references.citation: Cereb Cortex. 2000 Jun;10(6):614-20
references.pmid: 10859139
references.citation: Trends Neurosci. 2007 Mar;30(3):111-8
references.pmid: 17234277
references.citation: Proc Natl Acad Sci U S A. 2009 May 5;106(18):7281-8
references.pmid: 19342487
references.citation: Annu Rev Neurosci. 2000;23:473-500
references.pmid: 10845072
references.citation: Nat Neurosci. 2003 Jun;6(6):587-92
references.pmid: 12740581
references.citation: J Exp Psychol Anim Behav Process. 2001 Apr;27(2):115-24
references.pmid: 11296487
references.citation: J Neurosci. 2014 Jan 8;34(2):527-38
references.pmid: 24403152
references.citation: Cereb Cortex. 2008 Apr;18(4):968-77
references.pmid: 17702951
references.citation: PLoS One. 2010 Sep 15;5(9):e12751
references.pmid: 20856811
references.citation: Mol Psychiatry. 2007 Feb;12(2):120-50
references.pmid: 17160066
references.citation: Brain Res. 2001 Feb 16;892(1):86-93
references.pmid: 11172752
references.citation: Front Behav Neurosci. 2014 Apr 11;8:122
references.pmid: 24782730
references.citation: Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4572-7
references.pmid: 24591622
references.citation: Neurobiol Learn Mem. 2004 Jul;82(1):12-25
references.pmid: 15183167
references.citation: Pharmacol Biochem Behav. 2000 Jul;66(3):573-8
references.pmid: 10899372
references.citation: Cereb Cortex. 2014 Apr;24(4):845-58
references.pmid: 23183712
references.citation: Addict Biol. 2015 Jul;20(4):652-62
references.pmid: 24903743
references.citation: Trends Neurosci. 2011 Oct;34(10):536-47
references.pmid: 21851992
references.citation: Behav Brain Res. 2002 Dec 2;137(1-2):75-114
references.pmid: 12445717
references.citation: Learn Mem. 2004 Sep-Oct;11(5):485-94
references.pmid: 15466298
references.citation: Learn Mem. 2010 Feb 13;17(2):71-5
references.pmid: 20154351
references.citation: Hippocampus. 2015 Feb;25(2):149-58
references.pmid: 25160592
references.citation: Trends Neurosci. 2007 May;30(5):220-7
references.pmid: 17400299
references.citation: Hippocampus. 2006;16(2):174-82
references.pmid: 16358312