title: Methamphetamine-induced changes in the striatal dopamine pathway in μ-opioid receptor knockout mice.
abstract: BACKGROUND
  Repeated exposure to methamphetamine (METH) can cause not only neurotoxicity but also addiction. Behavioral sensitization is widely used as an animal model for the study of drug addiction. We previously reported that the μ-opioid receptor knockout mice were resistant to METH-induced behavioral sensitization but the mechanism is unknown.
  
  
  METHODS
  The present study determined whether resistance of the μ-opioid receptor (μ-OR) knockout mice to behavioral sensitization is due to differential expression of the stimulatory G protein α subunit (Gαs) or regulators of G-protein signaling (RGS) coupled to the dopamine D1 receptor. Mice received daily intraperitoneal injections of saline or METH (10 mg/kg) for 7 consecutive days to induce sensitization. On day 11(following 4 abstinent days), mice were either given a test dose of METH (10 mg/kg) for behavioral testing or sacrificed for neurochemical assays without additional METH treatment.
  
  
  RESULTS
  METH challenge-induced stereotyped behaviors were significantly reduced in the μ-opioid receptor knockout mice when compared with those in wild-type mice. Neurochemical assays indicated that there is a decrease in dopamine D1 receptor ligand binding and an increase in the expression of RGS4 mRNA in the striatum of METH-treated μ-opioid receptor knockout mice but not of METH-treated wild-type mice. METH treatment had no effect on the expression of Gαs and RGS2 mRNA in the striatum of either strain of mice.
  
  
  CONCLUSIONS
  These results indicate that down-regulation of the expression of the dopamine D1 receptor and up-regulation of RGS4 mRNA expression in the striatum may contribute to the reduced response to METH-induced stereotypy behavior in μ-opioid receptor knockout mice. Our results highlight the interactions of the μ-opioid receptor system to METH-induced behavioral responses by influencing the expression of RGS of dopamine D1 receptors.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA. spark@umc.edu
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Park
authors.forename: Xine
authors.initials: X
authors.lastname: Shen
authors.forename: Lu-Tai
authors.initials: LT
authors.lastname: Tien
authors.forename: Richard
authors.initials: R
authors.lastname: Roman
authors.forename: Tangeng
authors.initials: T
authors.lastname: Ma
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D059333:Central Nervous System Sensitization / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects
chemical_list: D044385:GTP-Binding Protein alpha Subunits; D020710:RGS Proteins; D017447:Receptors, Dopamine D1; D017450:Receptors, Opioid, mu; C105345:Rgs2 protein, mouse; C098799:RGS4 protein; D008694:Methamphetamine; D004298:Dopamine
references.citation: Pharmacol Rev. 2002 Sep;54(3):527-59
references.pmid: 12223533
references.citation: J Pharmacol Exp Ther. 1987 Jun;241(3):1120-4
references.pmid: 3110407
references.citation: J Neurosci Res. 2007 Feb 15;85(3):673-80
references.pmid: 17139685
references.citation: Neurobiol Dis. 2002 Aug;10(3):334-43
references.pmid: 12270694
references.citation: Neuropsychopharmacology. 1997 Jan;16(1):77-82
references.pmid: 8981391
references.citation: J Pharmacol Exp Ther. 1995 May;273(2):808-15
references.pmid: 7752084
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10451-6
references.pmid: 11517332
references.citation: J Neurochem. 1995 Dec;65(6):2706-15
references.pmid: 7595569
references.citation: Psychopharmacology (Berl). 1988;95(4):556-9
references.pmid: 3145527
references.citation: J Pharmacol Exp Ther. 1992 Apr;261(1):341-8
references.pmid: 1532835
references.citation: Brain Res Brain Res Rev. 1993 Sep-Dec;18(3):247-91
references.pmid: 8401595
references.citation: Science. 1990 Dec 7;250(4986):1429-32
references.pmid: 2147780
references.citation: Brain Res Mol Brain Res. 2005 Jan 5;133(1):162-5
references.pmid: 15661377
references.citation: Neuroreport. 2007 Aug 6;18(12):1261-5
references.pmid: 17632279
references.citation: J Neurochem. 1999 Apr;72(4):1529-33
references.pmid: 10098858
references.citation: Eur J Pharmacol. 1988 Mar 15;147(3):441-51
references.pmid: 3259931
references.citation: J Neurochem. 1998 May;70(5):2216-9
references.pmid: 9572311
references.citation: J Pharmacol Exp Ther. 2007 Nov;323(2):650-7
references.pmid: 17693584
references.citation: Brain Res Mol Brain Res. 1998 Mar 1;54(2):321-6
references.pmid: 9555078
references.citation: Addiction. 2000 Aug;95 Suppl 2:S91-117
references.pmid: 11002906
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2002 Oct;26(6):1177-83
references.pmid: 12452543
references.citation: Psychopharmacology (Berl). 1991;104(2):265-74
references.pmid: 1876671
references.citation: Life Sci. 1994;55(17):PL339-44
references.pmid: 7934637
references.citation: J Pharmacol Exp Ther. 1996 Mar;276(3):1022-9
references.pmid: 8786531
references.citation: J Neurochem. 2003 Mar;84(5):1118-27
references.pmid: 12603835
references.citation: Mol Psychiatry. 2001 May;6(3):293-301
references.pmid: 11326297
references.citation: Annu Rev Neurosci. 2006;29:565-98
references.pmid: 16776597
references.citation: Pharmacol Rev. 2011 Mar;63(1):182-217
references.pmid: 21303898
references.citation: Synapse. 2000 Jul;37(1):1-15
references.pmid: 10842346
references.citation: J Biomed Sci. 2006 Nov;13(6):797-811
references.pmid: 16847721
references.citation: J Neurochem. 1993 Sep;61(3):890-8
references.pmid: 8395565
references.citation: Curr Opin Pharmacol. 2007 Feb;7(1):77-85
references.pmid: 17085074
references.citation: Neuroscience. 1994 Dec;63(4):1111-6
references.pmid: 7700512
references.citation: FASEB J. 1995 Apr;9(7):516-25
references.pmid: 7737460
references.citation: Int J Physiol Pathophysiol Pharmacol. 2009 Sep 25;1(2):162-179
references.pmid: 20411028
references.citation: Neurotoxicology. 2010 Jun;31(3):326-30
references.pmid: 20184921
references.citation: Neuroscience. 2000;101(1):5-10
references.pmid: 11068131
references.citation: J Neurochem. 2006 Mar;96(6):1606-15
references.pmid: 16539683
references.citation: Brain Res Gene Expr Patterns. 2002 Oct;1(3-4):193-8
references.pmid: 12638131
references.citation: Proc Natl Acad Sci U S A. 1983 Jun;80(12):3841-4
references.pmid: 6190182
references.citation: J Neurosci Res. 2010 Aug 1;88(10):2294-302
references.pmid: 20209629
references.citation: J Neurosci. 1997 Oct 15;17(20):8024-37
references.pmid: 9315921
references.citation: Neuromolecular Med. 2005;7(1-2):101-27
references.pmid: 16052041
references.citation: Eur J Pharmacol. 1972 Apr;18(1):95-106
references.pmid: 4555563
references.citation: Eur J Pharmacol. 1988 Nov 22;157(2-3):125-33
references.pmid: 2975996
references.citation: Physiol Rev. 2009 Oct;89(4):1379-412
references.pmid: 19789384
references.citation: Nature. 1991 Apr 18;350(6319):614-9
references.pmid: 1826762
references.citation: Annu Rev Biochem. 2000;69:795-827
references.pmid: 10966476
references.citation: Life Sci. 1988;42(19):1841-5
references.pmid: 2966885
references.citation: Indian J Exp Biol. 2008 Oct;46(10):704-14
references.pmid: 19024168
references.citation: J Pharmacol Exp Ther. 1993 Jan;264(1):489-95
references.pmid: 8093731
references.citation: J Neurochem. 1993 Feb;60(2):566-71
references.pmid: 8419537
references.citation: Cell Signal. 2006 May;18(5):579-91
references.pmid: 16226429
references.citation: Pharmacol Rev. 2011 Jun;63(2):348-65
references.pmid: 21490129
references.citation: Neuropharmacology. 1986 Mar;25(3):331-4
references.pmid: 2871516
references.citation: Brain Res Mol Brain Res. 2001 Mar 31;88(1-2):113-23
references.pmid: 11295237
references.citation: J Biol Chem. 2003 Mar 21;278(12):10087-93
references.pmid: 12531899