title: Cocaine modulation of frontostriatal expression of Zif268, D2, and 5-HT2c receptors in high and low impulsive rats.
abstract: Impulsivity shares high comorbidity with substance abuse in humans, and high impulsivity (HI) in rats has been identified as a predictive factor for cocaine addiction-like behavior. Despite the evidence that high impulsivity is associated with altered function of corticostriatal networks, the specific neural substrates underlying the increased vulnerability of impulsive individuals to develop cocaine addiction remain unknown. We therefore investigated specific neural correlates of HI within the corticostriatal circuitry and determined how they interact with a protracted history of cocaine self-administration. We used in situ hybridization to map brain expression of two major genes implicated in impulsivity, encoding the dopamine D2 receptor (DA D2R) and the 5-HT2c receptor (5-HT2cR), and an immediate early gene associated with neuronal plasticity, zif268, in groups of rats selected for HI and low impulsivity (LI) on a 5-choice serial reaction time task (5-CSRTT) immediately after 5-CSRTT training, and following 10 or 50 days of cocaine self-administration. HI rats exhibited decreased DA D2R mRNA in the mesolimbic pathway, and increased 5-HT2cR mRNA in the orbitofrontal cortex compared with LI rats. HI rats also showed decreased zif268 mRNA in the ventral and dorsomedial striatum. Cocaine exposure decreased striatal D2R mRNA in both HI and LI rats, decreased 5-HT2cR mRNA differentially in striatal and prefrontal areas between HI and LI rats, and selectively decreased zif268 mRNA in the orbitofrontal and infralimbic cortices of HI animals. These findings implicate novel markers underlying the vulnerability of impulsive rats to cocaine addiction that localize to the OFC, infralimbic cortex, and striatum.
authors: Behavioral and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors: Morgane
authors: M
authors: Besson
authors: Yann
authors: Y
authors: Pelloux
authors: Ruth
authors: R
authors: Dilleen
authors: David Eh
authors: DE
authors: Theobald
authors: Alan
authors: A
authors: Lyon
authors: Aude
authors: A
authors: Belin-Rauscent
authors: Trevor W
authors: TW
authors: Robbins
authors: Jeffrey W
authors: JW
authors: Dalley
authors: Barry J
authors: BJ
authors: Everitt
authors: David
authors: D
authors: Belin
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects; D007175:Impulsive Behavior / Q000378:metabolism*; D008297:Male; D009434:Neural Pathways / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D044405:Receptor, Serotonin, 5-HT2C / Q000096:biosynthesis*; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis*; D012646:Self Administration
chemical_list: D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D044405:Receptor, Serotonin, 5-HT2C; D017448:Receptors, Dopamine D2; D003042:Cocaine
references: J Neurosci. 2006 May 3;26(18):4956-60
references: 16672671
references: Philos Trans R Soc Lond B Biol Sci. 2008 Oct 12;363(1507):3125-35
references: 18640910
references: Neurosci Biobehav Rev. 2003 Nov;27(7):623-37
references: 14624807
references: Prog Neurobiol. 2004 Nov;74(4):183-211
references: 15556287
references: Neuropsychopharmacology. 2008 Sep;33(10):2398-406
references: 18046307
references: Neurosci Biobehav Rev. 2008;32(4):777-810
references: 18295884
references: Science. 2004 Aug 13;305(5686):1014-7
references: 15310906
references: Brain Struct Funct. 2008 Sep;213(1-2):215-27
references: 18488248
references: Eur J Pharmacol. 2003 Nov 7;480(1-3):151-62
references: 14623358
references: Int J Neuropsychopharmacol. 2009 Apr;12(3):423-9
references: 19025723
references: Neuropharmacology. 2008 Nov;55(6):969-76
references: 18602407
references: Biol Psychiatry. 2008 Feb 1;63(3):256-62
references: 17719014
references: Ann N Y Acad Sci. 2007 Dec;1121:576-97
references: 17846151
references: Science. 2010 Jul 30;329(5991):532
references: 20671181
references: Psychopharmacology (Berl). 2002 Oct;163(3-4):362-80
references: 12373437
references: Science. 2008 Jun 6;320(5881):1352-5
references: 18535246
references: Psychopharmacology (Berl). 1997 Oct;133(4):329-42
references: 9372531
references: J Neurochem. 2006 Nov;99(4):1311-9
references: 17018023
references: Science. 2010 Jun 25;328(5986):1709-12
references: 20576893
references: Prog Brain Res. 2008;172:319-46
references: 18772040
references: Biol Psychiatry. 2008 Feb 1;63(3):301-8
references: 17884016
references: Neuron. 2008 Feb 7;57(3):432-41
references: 18255035
references: BMC Res Notes. 2009 May 05;2:71
references: 19416518
references: Neurosci Biobehav Rev. 2004 Jan;27(8):813-20
references: 15019430
references: Brain. 2011 Jul;134(Pt 7):2013-24
references: 21690575
references: J Neurosci. 2009 Nov 25;29(47):14734-40
references: 19940168
references: Behav Brain Res. 2011 Mar 1;217(2):454-62
references: 21073904
references: Neuron. 2011 Feb 24;69(4):680-94
references: 21338879
references: Addict Biol. 2010 Jul;15(3):227-49
references: 20456287
references: Prog Brain Res. 2008;172:543-65
references: 18772050
references: Neurosci Biobehav Rev. 2010 Jan;34(1):50-72
references: 19615404
references: Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5764-8
references: 1631058
references: Biol Psychiatry. 2009 May 15;65(10):851-6
references: 19181308
references: Nat Neurosci. 2006 Aug;9(8):1050-6
references: 16829955
references: J Neurosci. 2008 Jun 4;28(23):6046-53
references: 18524910
references: Science. 2004 Aug 13;305(5686):1017-9
references: 15310907
references: Neuropharmacology. 2000;39(1):123-32
references: 10665825
references: Mol Psychiatry. 2013 Jun;18(6):729-37
references: 22584869
references: Eur J Neurosci. 2009 Apr;29(8):1615-26
references: 19419424
references: Neuropsychopharmacology. 2011 Feb;36(3):569-79
references: 20980989
references: Neuropsychopharmacology. 2010 Mar;35(4):1026-39
references: 20072118
references: Cereb Cortex. 2007 Jan;17(1):18-27
references: 16481566
references: Science. 2007 Mar 2;315(5816):1267-70
references: 17332411
references: Neuroscience. 2012 Jul 26;215:42-58
references: 22542672
references: Pharmacol Biochem Behav. 2002 Apr;71(4):727-34
references: 11888564
references: Psychopharmacology (Berl). 2007 Sep;194(1):127-37
references: 17514480
references: Clin Psychol Rev. 2011 Apr;31(3):328-41
references: 21382538
references: Mol Psychiatry. 2004 Jun;9(6):557-69
references: 15098002
references: Biol Psychiatry. 2009 May 15;65(10):863-8
references: 18639867
references: Psychopharmacology (Berl). 2007 Sep;193(4):567-78
references: 17505818
references: J Pharmacol Exp Ther. 1993 Oct;267(1):496-505
references: 8229780
references: J Neurosci. 2010 Jan 20;30(3):930-8
references: 20089901
references: Neuropsychopharmacology. 2010 Jan;35(2):560-9
references: 19847161