Behavioral stress may increase the rewarding valence of cocaine-associated cues through a dynorphin/kappa-opioid receptor-mediated mechanism without affecting associative learning or memory retrieval mechanisms.
Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress (FSS) before cocaine develop significantly greater conditioned place preference (CPP) for the drug-paired chamber than unstressed mice. Analysis of the dose dependency showed that FSS increased both the maximal CPP response and sensitivity to cocaine. To determine whether FSS potentiated CPP by enhancing associative learning mechanisms, mice were conditioned with cocaine in the absence of stress, then challenged after association was complete with the kappa-opioid receptor (KOR) agonist U50,488 or repeated FSS, before preference testing. Mice challenged with U50,488 60 min before CPP preference testing expressed significantly greater cocaine-CPP than saline-challenged mice. Potentiation by U50,488 was dose and time dependent and blocked by the KOR antagonist norbinaltorphimine (norBNI). Similarly, mice subjected to repeated FSS before the final preference test expressed significantly greater cocaine-CPP than unstressed controls, and FSS-induced potentiation was blocked by norBNI. Novel object recognition (NOR) performance was not affected by U50,488 given 60 min before assay, but was impaired when given 15 min before NOR assay, suggesting that KOR activation did not potentiate CPP by facilitating memory retrieval or expression. The results from this study show that the potentiation of cocaine-CPP by KOR activation does not result from an enhancement of associative learning mechanisms and that stress may instead enhance the rewarding valence of cocaine-associated cues by a dynorphin-dependent mechanism.
Schindler
Abigail G
AG
Department of Pharmacology, University of Washington School of Medicine, Seattle, WA 98195-7280, USA.
Li
Shuang
S
Chavkin
Charles
C
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D001245:Association Learning / Q000187:drug effects* / Q000502:physiology; D001522:Behavior, Animal; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004399:Dynorphins / Q000378:metabolism*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D011939:Mental Recall / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D012201:Reward; D013315:Stress, Psychological / Q000503:physiopathology*; D013550:Swimming / Q000523:psychology
D018712:Analgesics, Non-Narcotic; D000779:Anesthetics, Local; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; D003042:Cocaine
Am J Psychiatry. 2007 Aug;164(8):1149-59
17671276
Nature. 1981 Jun 18;291(5816):591-3
6264311
Brain Res. 2010 Feb 16;1314:44-55
19716811
Nat Neurosci. 2002 Jul;5(7):625-6
12055635
J Neurosci. 2007 Oct 24;27(43):11614-23
17959804
Behav Brain Res. 1988 Oct;30(3):259-63
2846004
Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):19168-73
19864633
Neuroscience. 2008 Jun 2;153(4):1225-34
18436386
Mol Psychiatry. 2002;7(3):254-75
11920153
Addict Biol. 2007 Sep;12(3-4):227-462
17678505
Psychopharmacology (Berl). 2004 Nov;176(2):204-13
15112031
Neuroscience. 1998 Jul;85(2):375-82
9622237
Nat Neurosci. 2005 Nov;8(11):1442-4
16251985
J Pharmacol Exp Ther. 2007 Dec;323(3):838-45
17823306
Neurobiol Learn Mem. 2007 Jul;88(1):94-103
17374494
Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17145-50
18955698
J Neurosci. 2009 Apr 1;29(13):4293-300
19339623
J Biol Chem. 2007 Oct 12;282(41):29803-11
17702750
Neuropsychopharmacology. 2009 Nov;34(12):2609-17
19675537
Brain Res. 2001 Jul 20;908(1):86-92
11457434
Nature. 1998 Aug 20;394(6695):787-90
9723618
Psychopharmacology (Berl). 2001 Mar 1;154(2):213-20
11314684
Pharmacol Ther. 2009 Sep;123(3):353-70
19481570
Neurosci Biobehav Rev. 1995 Spring;19(1):39-51
7770196
Psychopharmacology (Berl). 2008 Sep;200(1):59-70
18575850
J Neurosci. 2008 Jan 9;28(2):407-14
18184783
Neuropsychopharmacology. 2006 Jun;31(6):1241-8
16123746
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13508-14
8942964
Neuropsychopharmacology. 2006 Sep;31(9):1928-37
16292317
Brain Res Brain Res Rev. 2000 Aug;33(1):13-33
10967352
J Pharmacol Exp Ther. 2006 Jan;316(1):440-7
16223871
Brain Res. 1995 Nov 6;698(1-2):46-52
8581502
Nature. 1977 Apr 21;266(5604):730-2
559941
Neuroreport. 2008 Sep 17;19(14):1417-22
18766023
Biol Psychiatry. 2008 Dec 1;64(11):982-8
18639235
Brain Res. 2004 Dec 31;1030(2):247-55
15571673
Psychopharmacology (Berl). 2005 Dec;183(3):331-40
16249907
Psychopharmacology (Berl). 1994 Feb;114(1):63-70
7846208
Eur J Pharmacol. 2007 Aug 13;569(1-2):84-9
17568579
NIDA Res Monogr. 1986;75:563-66
2829003
J Neurosci. 2001 Sep 15;21(18):7397-403
11549750
Psychopharmacology (Berl). 2009 Jan;202(1-3):3-14
18704369
Nature. 1993 Jun 3;363(6428):451-4
8099201
J Pharmacol Exp Ther. 2000 Dec;295(3):1031-42
11082438
Science. 1982 Jan 22;215(4531):413-5
6120570
PLoS One. 2009 Dec 31;4(12):e8528
20052275
J Neurosci. 2003 Jul 2;23(13):5674-83
12843270
Neuropsychopharmacology. 2006 Apr;31(4):787-94
16123754
Brain Res. 2010 Feb 16;1314:56-73
19782055
Pharmacol Biochem Behav. 1998 Jul;60(3):655-64
9678649
Behav Brain Res. 1988 Nov 1;31(1):47-59
3228475
Neuropeptides. 2006 Feb;40(1):47-56
16313958
Arch Gen Psychiatry. 2006 Mar;63(3):324-31
16520439
J Pharmacol Exp Ther. 2003 Apr;305(1):323-30
12649385
Annu Rev Psychol. 2008;59:29-53
18154498
Psychopharmacology (Berl). 2000 Jan;148(1):41-51
10663416
Science. 1986 Aug 15;233(4765):774-6
3016896
Behav Pharmacol. 1990;1(4):339-345
11175418
Prog Brain Res. 2000;125:363-7
11098672