title: Low- and high-cocaine locomotor responding rats differ in reinstatement of cocaine seeking and striatal mGluR5 protein expression.
abstract: Behavioral responsiveness to initial cocaine use varies among individuals and may contribute to differential vulnerability to cocaine addiction. Rats also exhibit individual differences in cocaine's effects and can be classified as low or high cocaine responders (LCRs or HCRs, respectively), based on their initial cocaine-induced locomotor activity (10 mg/kg, i.p.). Here, we used the extinction/reinstatement model to address whether or not LCRs and HCRs differ in (i) extinction/reinstatement of cocaine self-administration behavior and (ii) levels of metabotropic glutamate receptors (mGluRs) following these behaviors. During the earliest acquisition sessions, LCRs exhibited significantly greater cocaine intake (0.8 mg/kg/infusion) and cocaine-paired lever responding than HCRs, but intake and lever responding converged by the end of the cocaine self-administration portion of the study. LCRs and HCRs did not differ in cocaine seeking during the first extinction session and extinguished cocaine seeking similarly. HCRs exhibited greater reinstatement than LCRs to lower (2.5 and 5 mg/kg), but not higher (10 mg/kg), i.p. priming doses of cocaine. The effect of drug-paired cues on reinstatement following extinction was complex, with HCRs and LCRs showing the greater effect of cue depending on the order in which cue- and drug-primed tests were given. Western blot analysis revealed that mGluR5 heteromers were significantly higher in the dorsal striatum of HCRs than LCRs following reinstatement testing. Although our previous findings with the LCR/HCR model have uniformly supported the idea that lower initial cocaine-induced activation predicts more ready development of cocaine addiction-like behaviors, here, we show a more complex relationship with cocaine reinstatement.
authors: Department of Pharmacology, University of Colorado Anschutz Medical Campus, MS 8303, Aurora, CO 80045, USA. Electronic address: mu282003@yahoo.com.
authors: Diana L
authors: DL
authors: Simmons
authors: Department of Psychology, University of Colorado Denver, CB 173, PO Box 173364, Denver, CO 80217, USA. Electronic address: Bruce.Mandt@ucdenver.edu.
authors: Bruce H
authors: BH
authors: Mandt
authors: Department of Pharmacology, University of Colorado Anschutz Medical Campus, MS 8303, Aurora, CO 80045, USA. Electronic address: chrisng569@yahoo.com.
authors: Christopher M C
authors: CM
authors: Ng
authors: Department of Pharmacology, University of Colorado Anschutz Medical Campus, MS 8303, Aurora, CO 80045, USA. Electronic address: Toni.L.Richards@gmail.com.
authors: Toni L
authors: TL
authors: Richards
authors: Department of Pharmacology, University of Colorado Anschutz Medical Campus, MS 8303, Aurora, CO 80045, USA. Electronic address: Dorothy.Yamamoto@ucdenver.edu.
authors: Dorothy J
authors: DJ
authors: Yamamoto
authors: Department of Pharmacology, University of Colorado Anschutz Medical Campus, MS 8303, Aurora, CO 80045, USA; Neuroscience Program, University of Colorado Anschutz Medical Campus, MS 8303, Aurora, CO 80045, USA. Electronic address: Nancy.Zahniser@ucdenver.edu.
authors: Nancy R
authors: NR
authors: Zahniser
authors: Department of Psychology, University of Colorado Denver, CB 173, PO Box 173364, Denver, CO 80217, USA. Electronic address: Richard.Allen@ucdenver.edu.
authors: Richard M
authors: RM
authors: Allen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000473:pathology*; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5 / Q000235:genetics / Q000378:metabolism*; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D018765:Dopamine Uptake Inhibitors; D064529:Receptor, Metabotropic Glutamate 5; D003042:Cocaine
keywords: Cocaine self-administration; DA; DAT; Dorsal striatum; Extinction/reinstatement; HCR; Individual differences; LCR; LMA; Metabotropic glutamate receptors; NAc; dSTR; dopamine; dopamine transporter; dorsal striatum; high cocaine responder; locomotor activity; low cocaine responder; nucleus accumbens
references: Neuropharmacology. 2004;47 Suppl 1:214-26
references: 15464139
references: Neuropharmacology. 2010 Mar;58(3):605-12
references: 19951714
references: Neuropsychopharmacology. 2002 Apr;26(4):479-88
references: 11927172
references: J Neurosci. 2005 Apr 13;25(15):3932-9
references: 15829645
references: J Pharmacol Exp Ther. 2003 Apr;305(1):180-90
references: 12649367
references: Curr Opin Pharmacol. 2004 Feb;4(1):23-9
references: 15018835
references: Psychopharmacology (Berl). 1989;97(1):59-64
references: 2496428
references: Curr Opin Pharmacol. 2009 Feb;9(1):59-64
references: 19157986
references: Brain Res. 2009 Apr 24;1267:89-102
references: 19368820
references: Proc Natl Acad Sci U S A. 2003 May 13;100(10):6186-91
references: 12716966
references: Neuropsychopharmacology. 2006 Apr;31(4):778-86
references: 16123768
references: J Pharmacol Exp Ther. 2002 Sep;302(3):1201-11
references: 12183681
references: J Pharmacol Exp Ther. 2012 Jul;342(1):214-21
references: 22518023
references: J Neurosci. 2010 Jun 9;30(23):7984-92
references: 20534846
references: Neuropsychopharmacology. 2003 Dec;28(12):2089-101
references: 12902997
references: Neurosci Biobehav Rev. 2010 Nov;35(2):212-9
references: 20097224
references: Neuropharmacology. 2011 Jun;60(7-8):1017-41
references: 21036182
references: Neuropsychopharmacology. 2010 Sep;35(10):2021-36
references: 20555310
references: Drug Alcohol Depend. 2008 Nov 1;98(1-2):54-62
references: 18539407
references: J Pharmacol Exp Ther. 2002 Nov;303(2):608-15
references: 12388642
references: C R Biol. 2007 Apr;330(4):329-38
references: 17502289
references: Neuron. 2008 Feb 7;57(3):432-41
references: 18255035
references: Neurosci Lett. 2010 May 26;476(1):9-13
references: 20302913
references: Psychopharmacology (Berl). 2005 Apr;179(1):247-54
references: 15602687
references: Biol Psychiatry. 2009 Apr 15;65(8):717-20
references: 19100966
references: J Subst Abuse Treat. 2005 Mar;28(2):189-96
references: 15780549
references: Addict Biol. 2013 Jan;18(1):40-9
references: 22340009
references: J Neurosci. 2010 Sep 8;30(36):11973-82
references: 20826661
references: Nat Rev Neurosci. 2009 Aug;10(8):561-72
references: 19571793
references: Nature. 2001 Jul 12;412(6843):141-2
references: 11449260
references: Behav Brain Res. 2009 Sep 14;202(2):238-44
references: 19463707
references: J Pharmacol Exp Ther. 2009 Dec;331(3):985-97
references: 19729579
references: Biol Psychiatry. 2007 Jun 1;61(11):1296-305
references: 17239355
references: Prog Neuropsychopharmacol Biol Psychiatry. 2007 Apr 13;31(3):593-9
references: 17270333
references: Behav Neurosci. 2011 Feb;125(1):10-9
references: 21319882
references: Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20703-8
references: 23184975
references: Neuropsychopharmacology. 2009 Aug;34(9):2057-71
references: 19295507
references: Nat Neurosci. 2001 Sep;4(9):873-4
references: 11528416
references: Genes Brain Behav. 2011 Mar;10(2):199-209
references: 21029375
references: Drug Alcohol Depend. 2008 Jan 1;92(1-3):208-16
references: 17900822
references: Psychopharmacology (Berl). 2008 Dec;201(2):195-202
references: 18685831
references: Science. 1991 Mar 29;251(5001):1580-6
references: 2011738
references: Biol Psychiatry. 2012 Jun 1;71(11):978-86
references: 22137594
references: Pharmacol Biochem Behav. 2007 Jan;86(1):37-44
references: 17250883
references: J Neurosci. 2002 Jul 15;22(14):6247-53
references: 12122083
references: Mamm Genome. 2005 May;16(5):291-305
references: 16104378
references: Neurosci Lett. 2009 Mar 13;452(2):167-71
references: 19118598
references: Psychopharmacology (Berl). 2012 Feb;219(4):1089-97
references: 21863236
references: Ann N Y Acad Sci. 2011 Jan;1216:73-85
references: 21272012
references: Curr Psychiatry Rep. 2011 Oct;13(5):398-405
references: 21792580
references: Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1976-81
references: 11172061
references: Behav Pharmacol. 2009 Feb;20(1):67-77
references: 19125118