title: Changing mechanisms of opiate tolerance and withdrawal during early development: animal models of the human experience.
abstract: Human infants may be exposed to opiates through placental transfer from an opiate-using mother or through the direct administration of such drugs to relieve pain (e.g., due to illness or neonatal surgery). Infants of many species show physical dependence and tolerance to opiates. The magnitude of tolerance and the nature of withdrawal differ from those of the adult. Moreover, the mechanisms that contribute to the chronic effects of opiates are not well understood in the infant but include biological processes that are both common to and distinct from those of the adult. We review the animal research literature on the effects of chronic and acute opiate exposure in infants and identify mechanisms of withdrawal and tolerance that are similar to and different from those understood in adults. These mechanisms include opioid pharmacology, underlying neural substrates, and the involvement of other neurotransmitter systems. It appears that brain circuitry and opioid receptor types are similar but that NMDA receptor function is immature in the infant. Intracellular signaling cascades may differ but data are complicated by differences between the effects of chronic versus acute morphine treatment. Given the limited treatment options for the dependent infant patient, further study of the biological functions that are altered by chronic opiate treatment is necessary to guide evidenced-based treatment modalities.
authors: Gordon A
authors: GA
authors: Barr
authors: Anika
authors: A
authors: McPhie-Lalmansingh
authors: Jessica
authors: J
authors: Perez
authors: Michelle
authors: M
authors: Riley
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use; D000818:Animals; D001921:Brain; D006801:Humans; D023421:Models, Animal; D009293:Opioid-Related Disorders; D010146:Pain
chemical_list: D000701:Analgesics, Opioid
references: Psychoneuroendocrinology. 2002 Jan-Feb;27(1-2):273-83
references: 11750783
references: Ann Ist Super Sanita. 1993;29(3):419-29
references: 8172461
references: J Pain. 2007 Aug;8(8):657-66
references: 17553749
references: Eur J Pharmacol. 1992 Apr 29;215(1):35-42
references: 1516648
references: Pharmacol Biochem Behav. 1997 Aug;57(4):779-83
references: 9259006
references: AAPS J. 2008 Dec;10(4):537-51
references: 18989788
references: Brain Res Brain Res Rev. 1999 Nov;30(3):289-304
references: 10567729
references: Pain. 2005 Aug;116(3):276-288
references: 15964684
references: Arch Dis Child Fetal Neonatal Ed. 2004 Sep;89(5):F390-3
references: 15321955
references: Dev Med Child Neurol. 1992 Feb;34(2):155-63
references: 1733821
references: Brain Res Dev Brain Res. 1991 May 20;60(1):99-102
references: 1914149
references: Curr Opin Support Palliat Care. 2010 Mar;4(1):1-5
references: 20019618
references: Psychopharmacology (Berl). 2000 Jun;150(3):325-36
references: 10923761
references: Int J Neuropsychopharmacol. 2003 Sep;6(3):253-65
references: 12974992
references: Pain. 2004 Jul;110(1-2):281-9
references: 15275778
references: J Pharmacol Exp Ther. 2000 Aug;294(2):531-8
references: 10900229
references: Eur J Pharmacol. 1995 Dec 27;294(1):297-301
references: 8788444
references: Cochrane Database Syst Rev. 2002;(3):CD002053
references: 12137641
references: Am J Psychiatry. 1993 Mar;150(3):423-8
references: 8434657
references: Pharmacol Biochem Behav. 2002 Nov;73(4):821-8
references: 12213527
references: J Addict Dis. 2010 Apr;29(2):175-91
references: 20407975
references: Jpn J Pharmacol. 2002 Nov;90(3):270-5
references: 12499582
references: J Pain. 2008 Jan;9(1):11-9
references: 17950674
references: Dev Med Child Neurol. 2004 Oct;46(10):700-5
references: 15473175
references: Neuropsychopharmacology. 2002 Mar;26(3):301-10
references: 11850145
references: J Neurosci. 2005 Feb 9;25(6):1366-74
references: 15703390
references: Am J Ther. 2010 Sep-Oct;17(5):498-510
references: 20844348
references: Neurosci Lett. 2006 May 29;400(1-2):154-7
references: 16517072
references: Pharmacol Biochem Behav. 2000 Jun;66(2):419-24
references: 10880699
references: Neurosci Lett. 1995 Jan 2;183(1-2):79-82
references: 7746492
references: ILAR J. 2006;47(1):39-48
references: 16391430
references: Cell Mol Neurobiol. 2008 Feb;28(2):157-72
references: 18041576
references: Brain Res Dev Brain Res. 1990 Jun 1;54(1):63-9
references: 2163782
references: J Pharmacol Exp Ther. 1997 Apr;281(1):514-21
references: 9103539
references: Life Sci. 1982 Sep 20-27;31(12-13):1393-6
references: 6292634
references: Experientia. 1992 Apr 15;48(4):322-33
references: 1582492
references: Cochrane Database Syst Rev. 2002;(3):CD002059
references: 12137642
references: Mol Neurobiol. 2009 Oct;40(2):101-7
references: 19468867
references: Brain Res. 2007 Apr 20;1142:28-36
references: 17300766
references: Trends Pharmacol Sci. 2001 Aug;22(8):404-8
references: 11479002
references: Neurotoxicol Teratol. 1990 May-Jun;12(3):183-9
references: 2164624
references: Psychopharmacology (Berl). 2000 Jun;150(3):253-9
references: 10923752
references: Brain Res. 1994 Apr 11;642(1-2):153-9
references: 7518322
references: Psychopharmacology (Berl). 2001 May;155(3):242-50
references: 11432686
references: Synapse. 2001 Feb;39(2):139-51
references: 11180501
references: Pediatrics. 2001 Feb;107(2):309-17
references: 11158464
references: Pain. 2003 Aug;104(3):437-447
references: 12927616
references: Pain. 2004 Jul;110(1-2):269-80
references: 15275777
references: Neurobehav Toxicol. 1979 Spring;1(1):33-40
references: 551300
references: Brain Res Dev Brain Res. 2000 Nov 30;124(1-2):73-80
references: 11113514
references: Eur J Pharmacol. 1984 Nov 13;106(2):231-9
references: 6152216
references: Psychopharmacology (Berl). 2000 Aug;151(2-3):121-41
references: 10972459
references: Exp Neurol. 1981 Aug;73(2):430-9
references: 6266859
references: Neurosci Lett. 2006 Oct 16;407(1):64-9
references: 16949209
references: J Paediatr Child Health. 2002 Feb;38(1):66-71
references: 11869404
references: Psychopharmacology (Berl). 1994 Jan;113(3-4):422-8
references: 7862854
references: Neurosci Lett. 2009 Dec 11;466(3):144-8
references: 19788914
references: Rev Neurosci. 2006;17(4):393-402
references: 17139840
references: Sleep. 1988 Apr;11(2):121-30
references: 3381053
references: Science. 1980 Jun 6;208(4448):1174-6
references: 7375928
references: Neuroreport. 2000 Feb 28;11(3):587-91
references: 10718319
references: Am J Addict. 2010 Nov-Dec;19(6):467-73
references: 20958840
references: Pediatr Res. 2000 Jun;47(6):727-35
references: 10832729
references: AAPS J. 2005 Oct 19;7(3):E587-91
references: 16353937
references: Int J Dev Neurosci. 2004 Aug-Oct;22(5-6):379-95
references: 15380837
references: Brain Res. 2008 Mar 14;1199:82-90
references: 18267316
references: Pharmacology. 2002 Sep;66(1):11-8
references: 12169760
references: Neuropsychopharmacology. 1995 Dec;13(4):301-7
references: 8747754
references: Brain Res Dev Brain Res. 1991 Dec 17;64(1-2):19-26
references: 1664787
references: Rev Neurosci. 2005;16(3):255-76
references: 16323564
references: Am J Physiol. 1990 Jun;258(6 Pt 2):R1453-8
references: 2163223
references: J Pharmacol Exp Ther. 1992 May;261(2):669-77
references: 1578378
references: Neuropsychopharmacology. 1995 Dec;13(4):347-56
references: 8747759
references: Pediatrics. 2010 May;125(5):e1208-25
references: 20403936
references: J Pharmacol Exp Ther. 1995 Jun;273(3):1361-74
references: 7791109
references: Eur J Pharmacol. 2004 Oct 1;500(1-3):121-8
references: 15464026
references: J Perinatol. 2000 Dec;20(8 Pt 2):S37-44
references: 11190699
references: Physiol Behav. 1982 Jan;28(1):5-7
references: 6281819
references: Dev Psychobiol. 1981 Sep;14(5):415-23
references: 6268473
references: Dev Psychobiol. 2009 Nov;51(7):544-52
references: 19708041
references: Eur J Pharmacol. 1997 Dec 11;340(2-3):161-7
references: 9537810
references: Brain Res. 1986 Oct;394(2):145-52
references: 3021285
references: Pharmacol Biochem Behav. 1998 May;60(1):97-104
references: 9610930
references: Obstet Gynecol Surv. 2007 Nov;62(11):749-57
references: 17925048
references: Psychopharmacology (Berl). 1989;98(4):530-4
references: 2505294
references: Dev Psychobiol. 2002 Mar;40(2):104-15
references: 11857325
references: Ir Med J. 1999 Jan-Feb;92(1):232-3, 236
references: 10360095
references: Pain. 2006 Apr;121(3):232-240
references: 16516386
references: Pediatr Crit Care Med. 2008 Nov;9(6):573-80
references: 18838937
references: Behav Neurosci. 1995 Dec;109(6):1189-98
references: 8748967
references: Neurosci Lett. 2009 Feb 13;451(1):89-93
references: 19111903
references: Neuropsychopharmacology. 1995 Dec;13(4):315-22
references: 8747756
references: Brain Res Dev Brain Res. 2003 Jan 10;140(1):117-25
references: 12524182
references: Synapse. 2000 Jun 15;36(4):254-66
references: 10819903
references: Brain Res. 1988 Jun 1;469(1-2):129-33
references: 2841016
references: Arch Med Res. 1996 Summer;27(2):139-44
references: 8696055
references: Psychopharmacologia. 1973;28(1):27-34
references: 4714678
references: Psychopharmacology (Berl). 1995 Apr;118(4):361-8
references: 7568621
references: Eur J Pharmacol. 1995 Dec 27;294(1):289-96
references: 8788443
references: Neuroreport. 2003 Aug 26;14(12):1603-7
references: 14502084
references: J Auton Nerv Syst. 1996 Jun 10;59(1-2):75-82
references: 8816368
references: Brain Res. 2000 Feb 21;856(1-2):227-35
references: 10677630
references: Brain Res Bull. 2004 May 30;63(4):339-49
references: 15196660
references: J Neurosci. 1985 Mar;5(3):584-8
references: 2983043
references: J Pharmacol Exp Ther. 1998 Feb;284(2):455-9
references: 9454784
references: Neuroscience. 2007 Jan 5;144(1):247-62
references: 17055659
references: Am J Drug Alcohol Abuse. 1992;18(3):275-87
references: 1329491
references: J Neurosci. 2006 Nov 15;26(46):12033-42
references: 17108177
references: J Addict Dis. 2010 Apr;29(2):259-76
references: 20407981
references: Neurosci Biobehav Rev. 2009 Sep;33(8):1192-7
references: 19747597
references: Neonatal Netw. 1995 Mar;14(2):39-48
references: 7746239
references: Neuron. 1993 Dec;11(6):995-1006
references: 8274284
references: Neuroinformatics. 2007 Spring;5(1):79-94
references: 17426354
references: NIDA Res Monogr. 1986;75:567-70
references: 3123976