Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation.
Mechanisms of opioid tolerance have focused on adaptive modifications within cells containing opioid receptors, defined here as cellular allostasis, emphasizing regulation of the opioid receptor signalosome. We review additional regulatory and opponent processes involved in behavioral tolerance, and include mechanistic differences both between agonists (agonist bias), and between μ- and δ-opioid receptors. In a process we will refer to as pass-forward allostasis, cells modified directly by opioid drugs impute allostatic changes to downstream circuitry. Because of the broad distribution of opioid systems, every brain cell may be touched by pass-forward allostasis in the opioid-dependent/tolerant state. We will implicate neurons and microglia as interactive contributors to the cumulative allostatic processes creating analgesic and hedonic tolerance to opioid drugs.
Department of Anesthesiology and Perioperative Care, University of California, Irvine, 837 Health Sciences Road, Irvine, CA 92697, USA.
Catherine M
CM
Cahill
Hatos Center for Neuropharmacology, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, 675 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
Wendy
W
Walwyn
Hatos Center for Neuropharmacology, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, 675 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
Anna M W
AMW
Taylor
Department of Psychiatry, University of Illinois at Chicago, 1601 West Taylor Street, Chicago, IL 60612, USA.
Amynah A A
AAA
Pradhan
Hatos Center for Neuropharmacology, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, 675 Charles E. Young Drive South, Los Angeles, CA 90095, USA. Electronic address: cevans@ucla.edu.
Christopher J
CJ
Evans
D052636:Allostasis / Q000502:physiology*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D004361:Drug Tolerance / Q000502:physiology*; D006801:Humans; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism
D000701:Analgesics, Opioid; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
arrestin; bias signaling; dopamine; microglia; opponent processes; reward; μ opioid receptor
J Neurosci. 2014 Mar 19;34(12):4239-50
24647944
Science. 1982 Apr 23;216(4544):436-7
7200260
CNS Neurosci Ther. 2014 Aug;20(8):728-36
24629168
Addict Biol. 2016 Nov;21(6):1086-1096
26096355
Neuropsychopharmacology. 2012 Jul;37(8):1953-62
22491351
Synapse. 2002 Dec 15;46(4):271-9
12373743
J Pharmacol Exp Ther. 2005 Sep;314(3):1195-201
15917400
Neuropsychopharmacology. 2013 Jul;38(8):1585-97
23446450
Neuron. 2015 Jun 3;86(5):1145-57
26050034
Neuron. 2007 Feb 15;53(4):577-89
17296558
J Neurosci. 2010 Nov 17;30(46):15400-8
21084596
Annu Rev Psychol. 2008;59:29-53
18154498
Mol Pharmacol. 2013 Dec;84(6):844-53
24061856
J Neurosci. 2014 Jun 4;34(23):7899-909
24899712
Nature. 2000 Dec 7;408(6813):720-3
11130073
Nature. 2000 Jan 27;403(6768):430-4
10667795
J Neurosci. 2014 Oct 15;34(42):13906-10
25319687
Curr Opin Neurobiol. 2013 Aug;23(4):559-63
23628232
Pain Physician. 2014 Jul-Aug;17(4):E503-7
25054400
Biol Psychiatry. 2013 Apr 15;73(8):729-37
23384483
Crit Rev Neurobiol. 2005;17(1):1-26
16307525
Anesthesiology. 2011 Dec;115(6):1363-81
22020140
Neuropharmacology. 2012 Jun;62(8):2463-71
22410393
Eur J Neurosci. 2001 Mar;13(5):1009-15
11264674
J Cell Sci. 2010 Dec 15;123(Pt 24):4259-70
21098639
Neuropsychopharmacology. 2014 Jul;39(8):1968-77
24561386
Neuron. 2012 Nov 21;76(4):790-803
23177963
Proc Natl Acad Sci U S A. 2012 Feb 14;109 (7):E442-51
22308427
Traffic. 2011 Feb;12(2):170-84
21106040
Neuron. 2015 Dec 16;88(6):1227-39
26671460
Science. 2006 Feb 17;311(5763):1017-20
16484499
J Biol Chem. 2007 Jul 13;282(28):20634-46
17500066
J Neurosci. 2003 Sep 10;23(23):8360-9
12967998
Neuron. 2016 Mar 16;89(6):1157-72
26985723
Science. 2009 Jun 26;324(5935):1732-4
19478142
J Neurosci. 2010 Dec 8;30(49):16459-68
21147985
Biol Psychiatry. 2014 Nov 15;76(10):760-2
25442057
Pharmacol Rev. 2016 Jul;68(3):631-700
27343248
EMBO J. 2002 Apr 2;21(7):1628-37
11927547
Drug Alcohol Depend. 2015 Aug 1;153:314-22
26059463
Nat Med. 2013 Nov;19(11):1524-8
24097188
Trends Neurosci. 2015 Apr;38(4):217-25
25637939
Nature. 2005 Dec 15;438(7070):1017-21
16355225
Brain Res. 2010 Feb 16;1314:44-55
19716811
F1000Res. 2016 Jul 19;5:null
27508068
Neuropsychopharmacology. 2014 Oct;39(11):2646-53
24853771
Neuropsychopharmacology. 2011 Feb;36(3):664-76
21068718
J Neurosci. 2016 May 25;36(21):5748-62
27225765
Nat Neurosci. 2009 Jan;12(1):77-84
19043410
J Neurosci. 2003 Oct 15;23(28):9305-11
14561857
Curr Opin Neurol. 2016 Jun;29(3):314-9
27023737
Neuropsychopharmacology. 2016 Jan;41(1):373-4
26657953
Clin J Pain. 2010 Jan;26 Suppl 10:S10-5
20026960
Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):E255-64
21670308
Nature. 2007 Jun 28;447(7148):1111-5
17522629
Cell Rep. 2013 Nov 27;5(4):1010-21
24239352
Neurobiol Dis. 2013 Nov;59:220-9
23911767
N Engl J Med. 2016 Mar 31;374(13):1253-63
27028915
Neuron. 2015 Sep 2;87(5):1063-77
26335648
Neuroscientist. 2009 Feb;15(1):90-104
19218233
Psychopharmacology (Berl). 2001 Mar 1;154(2):131-42
11314675
Trends Pharmacol Sci. 2009 Nov;30(11):581-91
19762094
Neuroscience. 2014 Sep 26;277:595-609
25086313
J Neurosci Res. 2014 Jul;92(7):937-43
24753218
Neuropsychopharmacology. 2015 Aug;40(9):2057-8
26174493
Behav Brain Res. 2002 Feb 1;129(1-2):17-29
11809491
J Neurosci. 2013 Jan 16;33(3):961-71
23325235
Int J Neuropsychopharmacol. 2013 Jun;16(5):1165-7
23110855
Nat Rev Neurosci. 2009 Aug;10(8):561-72
19571793
Addict Biol. 2015 Mar;20(2):275-84
24330252
J Neurosci. 2007 May 9;27(19):5092-104
17494695
Neuron. 2014 Jun 18;82(6):1346-56
24857021
PLoS One. 2012;7(5):e36871
22590628
J Neurosci. 2011 Dec 7;31(49):17835-47
22159099
Pain. 2016 Jun;157(6):1194-8
26797678
Cold Spring Harb Perspect Med. 2012 Jul;2(7):a012070
22762025
Pain. 2010 Sep;150(3):401-13
20573450
Pharmacol Rev. 2016 Apr;68(2):419-57
26956246
Front Hum Neurosci. 2014 Mar 28;8:174
24734015
Nat Neurosci. 2016 May;19(5):725-33
27019014
Nat Neurosci. 2013 Feb;16(2):183-92
23292683
Cell Signal. 2015 Sep;27(9):1799-806
26056051
Pharmacol Rev. 2013 Jan 15;65(1):223-54
23321159
J Appl Physiol (1985). 2014 Oct 15;117(8):857-68
25103966
Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11202-7
8855333
J Neurosci. 2012 Aug 15;32(33):11187-200
22895704
J Neurosci. 2003 Sep 10;23(23):8237-46
12967985
Eur J Pharmacol. 2012 Jun 15;685(1-3):133-40
22521552
Front Pharmacol. 2014 Nov 17;5:253
25452729
Nat Neurosci. 2004 Feb;7(2):160-9
14730310
Brain Res. 2014 May 27;1565:28-36
24721524
Neuroscience. 2015 Jan 22;284:107-24
25290009
Nat Neurosci. 2014 Feb;17(2):254-61
24413699
Pharmacol Biochem Behav. 2015 Aug;135:192-8
26071679
J Pain. 2015 Sep;16(9):887-94
26101814
Nature. 2011 Jun 29;475(7356):377-80
21716290
Neuropharmacology. 2011 Jan;60(1):58-65
20713067
Curr Opin Cell Biol. 2014 Apr;27:109-16
24680436
Brain Behav Immun. 2012 Feb;26(2):318-25
22004988
Brain Res Bull. 2013 Jan;90:92-9
23069789
West Indian Med J. 2013 Mar;62(3):210-5
24564042
Pain. 2014 Sep;155(9):1829-35
24954166
Eur J Neurosci. 2012 Jan;35(2):279-90
22236063
J Neurosci. 2015 Jun 3;35(22):8442-50
26041913
Br J Pharmacol. 2015 Jan;172(2):492-500
24597632
Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19407-12
22084102
J Neurosci. 2015 Sep 16;35(37):12917-31
26377476
J Neurosci. 2016 Mar 23;36(12):3541-51
27013682
Eur J Neurosci. 2013 Mar;37(6):996-1003
23279128
Br J Pharmacol. 2012 Nov;167(5):960-9
22708627
Proc Natl Acad Sci U S A. 2016 Jan 19;113(3):757-62
26739562
Psychopharmacology (Berl). 1984;84(2):167-73
6438676
Nature. 2016 Feb 11;530(7589):219-22
26840481
Pharmacol Biochem Behav. 1998 Jan;59(1):1-17
9443530
J Neurosci. 2011 May 18;31(20):7533-9
21593338
J Neurosci. 2011 May 11;31(19):7122-30
21562274
J Neurosci. 2004 Aug 18;24(33):7353-65
15317861
Cell Rep. 2016 Mar 29;14 (12 ):2774-83
26997280
Psychopharmacology (Berl). 1997 Oct;133(3):240-8
9361329
Brain Res Brain Res Rev. 1998 Dec;28(3):309-69
9858756
Neuropsychopharmacology. 2016 Mar;41(4):949-59
26202104
Addict Biol. 2013 May;18(3):480-95
22804800
Nature. 1996 Oct 31;383(6603):819-23
8893006
J Neurosci Res. 2012 Jun;90(6):1270-83
22388870
J Biol Chem. 2010 May 7;285(19):14318-29
20207744
Neuropharmacology. 2014 Jan;76 Pt B:370-82
23747571
J Neuroimmunol. 1998 Mar 15;83(1-2):70-6
9610675
Science. 2012 Oct 5;338(6103):124-8
23042896