title: Dopamine D(3) receptor deletion or blockade attenuates cocaine-induced conditioned place preference in mice.
abstract: The dopamine (DA) D3 receptor (D3R) has received much attention in medication development for treatment of addiction. However, the functional role of the D3R in drug reward and addiction has been a matter of debate. We recently reported that D3 receptor-knockout (D3(-/-)) mice display increased vulnerability to cocaine self-administration, which we interpret as a compensatory response to attenuated cocaine reward after D3R deletion. Here we report that D3(-/-) mice displayed attenuated cocaine-induced conditioned place response (CPP) compared to wild-type mice. Similarly, blockade of brain D3Rs by YQA-14, a novel DA D3 receptor antagonist, significantly and dose-dependently inhibits acquisition and expression of cocaine-induced CPP in WT mice, but not in D3(-/-) mice. These findings suggest that: 1) D3Rs play an important role in mediating cocaine's rewarding effects; and 2) YQA-14 is a highly potent and selective D3R antagonist in vivo, which deserves further study as a candidate for treatment of cocaine addiction.
authors: Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
authors: Rui
authors: R
authors: Song
authors: Hai-Ying
authors: HY
authors: Zhang
authors: Xiao-Qing
authors: XQ
authors: Peng
authors: Rui-Bin
authors: RB
authors: Su
authors: Ri-Fang
authors: RF
authors: Yang
authors: Jin
authors: J
authors: Li
authors: Zheng-Xiong
authors: ZX
authors: Xi
authors: Eliot L
authors: EL
authors: Gardner
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010879:Piperazines / Q000494:pharmacology; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics
chemical_list: D001583:Benzoxazoles; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D050637:Receptors, Dopamine D3; C571881:YQA14; D003042:Cocaine
references: Neuroreport. 1997 Jul 7;8(9-10):2373-7
references: 9243643
references: Trends Pharmacol Sci. 1994 Jul;15(7):264-70
references: 7940991
references: J Neurosci. 1996 Oct 1;16(19):6100-6
references: 8815892
references: Behav Pharmacol. 1995 Jun;6(4):333-347
references: 11224342
references: J Neurosci. 2007 Nov 28;27(48):13140-50
references: 18045908
references: Neuropsychopharmacology. 2004 Aug;29(8):1479-87
references: 15100700
references: Eur J Neurosci. 2005 Jun;21(12):3427-38
references: 16026480
references: Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17675-80
references: 23045656
references: J Pharmacol Exp Ther. 1995 Dec;275(3):1355-66
references: 8531103
references: Neuron. 1997 Oct;19(4):837-48
references: 9354330
references: Neuron. 2011 Feb 24;69(4):628-49
references: 21338876
references: Neuroscience. 2011 Mar 10;176:152-61
references: 21168475
references: J Neurosci. 2002 Nov 1;22(21):9595-603
references: 12417684
references: Eur J Neurosci. 2002 Jun;15(12):2016-26
references: 12099907
references: Neuropsychopharmacology. 2006 Jul;31(7):1393-405
references: 16205781
references: Psychopharmacology (Berl). 1996 May;125(1):13-22
references: 8724444
references: Neuropharmacology. 2004 Dec;47(8):1117-34
references: 15567422
references: Synapse. 1999 Mar 1;31(3):210-5
references: 10029239
references: Science. 1993 Jun 18;260(5115):1814-6
references: 8099761
references: Pharmacol Rev. 2011 Mar;63(1):182-217
references: 21303898
references: J Pharmacol Exp Ther. 1996 Sep;278(3):1128-37
references: 8819495
references: J Neurochem. 2010 Jul;114(2):530-41
references: 20456009
references: Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1945-9
references: 8700864
references: Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8155-9
references: 1518841
references: Pharmacol Biochem Behav. 2002 Jun;72(3):623-32
references: 12175459
references: Neuroscience. 1995 Apr;65(3):731-45
references: 7609872
references: Brain Res. 1991 Nov 15;564(2):203-19
references: 1839781
references: Curr Opin Neurobiol. 1996 Apr;6(2):243-51
references: 8725967
references: J Neurosci. 2002 Apr 1;22(7):2977-88
references: 11923462
references: Exp Clin Psychopharmacol. 2012 Oct;20(5):352-63
references: 22867038
references: Ann N Y Acad Sci. 1999 Jun 29;877:507-22
references: 10415668
references: Addict Biol. 2012 Mar;17(2):259-73
references: 21507153
references: Mol Psychiatry. 1997 Jan;2(1):5-6
references: 9154208
references: Arzneimittelforschung. 1992 Feb;42(2A):224-30
references: 1586393
references: Psychopharmacology (Berl). 1996 Apr;124(4):306-14
references: 8739545
references: Neuropharmacology. 1999 Apr;38(4):555-65
references: 10221759