title: The dissection of transcriptional modules regulated by various drugs of abuse in the mouse striatum.
abstract: BACKGROUND
  Various drugs of abuse activate intracellular pathways in the brain reward system. These pathways regulate the expression of genes that are essential to the development of addiction. To reveal genes common and distinct for different classes of drugs of abuse, we compared the effects of nicotine, ethanol, cocaine, morphine, heroin and methamphetamine on gene expression profiles in the mouse striatum.
  
  
  RESULTS
  We applied whole-genome microarray profiling to evaluate detailed time-courses (1, 2, 4 and 8 hours) of transcriptome alterations following acute drug administration in mice. We identified 42 drug-responsive genes that were segregated into two main transcriptional modules. The first module consisted of activity-dependent transcripts (including Fos and Npas4), which are induced by psychostimulants and opioids. The second group of genes (including Fkbp5 and S3-12), which are controlled, in part, by the release of steroid hormones, was strongly activated by ethanol and opioids. Using pharmacological tools, we were able to inhibit the induction of particular modules of drug-related genomic profiles. We selected a subset of genes for validation by in situ hybridization and quantitative PCR. We also showed that knockdown of the drug-responsive genes Sgk1 and Tsc22d3 resulted in alterations to dendritic spines in mice, possibly reflecting an altered potential for plastic changes.
  
  
  CONCLUSIONS
  Our study identified modules of drug-induced genes that share functional relationships. These genes may play a critical role in the early stages of addiction.
authors.affiliation: Department of Molecular Neuropharmacology, Institute of Pharmacology PAS, Smetna 12, Krakow, 31-343, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Piechota
authors.forename: Michal
authors.initials: M
authors.lastname: Korostynski
authors.forename: Wojciech
authors.initials: W
authors.lastname: Solecki
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gieryk
authors.forename: Michal
authors.initials: M
authors.lastname: Slezak
authors.forename: Wiktor
authors.initials: W
authors.lastname: Bilecki
authors.forename: Barbara
authors.initials: B
authors.lastname: Ziolkowska
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kostrzewa
authors.forename: Iwona
authors.initials: I
authors.lastname: Cymerman
authors.forename: Lukasz
authors.initials: L
authors.lastname: Swiech
authors.forename: Jacek
authors.initials: J
authors.lastname: Jaworski
authors.forename: Ryszard
authors.initials: R
authors.lastname: Przewlocki
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001665:Binding Sites; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D033481:Chromosomes, Mammalian / Q000235:genetics; D016000:Cluster Analysis; D049229:Dendritic Spines / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks / Q000187:drug effects*; D013287:Illicit Drugs / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012201:Reward; D019966:Substance-Related Disorders / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000697:Central Nervous System Stimulants; D013287:Illicit Drugs; D012333:RNA, Messenger; D014157:Transcription Factors
references.citation: J Neurosci. 2005 May 18;25(20):4996-5003
references.pmid: 15901780
references.citation: Learn Mem. 2006 Mar-Apr;13(2):114-8
references.pmid: 16585788
references.citation: J Neurosci. 1999 Apr 1;19(7):2789-98
references.pmid: 10087090
references.citation: Lancet. 2007 Mar 24;369(9566):1047-53
references.pmid: 17382831
references.citation: Science. 1987 Jul 10;237(4811):192-7
references.pmid: 3037702
references.citation: Neurosci Lett. 1990 Dec 11;120(2):271-4
references.pmid: 2127308
references.citation: Nature. 2008 Mar 27;452(7186):423-8
references.pmid: 18344981
references.citation: Science. 1986 Oct 3;234(4772):80-3
references.pmid: 3749894
references.citation: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D91-4
references.pmid: 14681366
references.citation: Psychopharmacology (Berl). 1991;103(2):187-96
references.pmid: 2027920
references.citation: Synapse. 2003 Jun 15;48(4):157-69
references.pmid: 12687634
references.citation: J Neurosci. 1994 Sep;14(9):5623-34
references.pmid: 8083758
references.citation: Brain Res Mol Brain Res. 2003 Apr 10;112(1-2):113-25
references.pmid: 12670709
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5549-54
references.pmid: 16569693
references.citation: Mol Biol Cell. 1993 Sep;4(9):897-906
references.pmid: 7903056
references.citation: Nat Protoc. 2009;4(8):1184-91
references.pmid: 19617889
references.citation: Hum Mol Genet. 1999;8(10):1821-32
references.pmid: 10469833
references.citation: Nature. 1997 Nov 27;390(6658):401-4
references.pmid: 9389479
references.citation: J Pharmacol Exp Ther. 2002 Jun;301(3):785-9
references.pmid: 12023504
references.citation: PLoS Genet. 2006 Jan;2(1):e6
references.pmid: 16424919
references.citation: Behav Genet. 1996 May;26(3):313-23
references.pmid: 8754254
references.citation: Science. 2004 Mar 26;303(5666):2011-5
references.pmid: 14976264
references.citation: Neuroscience. 1994 Jul;61(1):81-91
references.pmid: 7969898
references.citation: Eur J Neurosci. 2008 Jun;27(11):2973-84
references.pmid: 18588537
references.citation: Genome Biol. 2007;8(6):R128
references.pmid: 17598886
references.citation: Nat Med. 2006 Jun;12(6):677-81
references.pmid: 16715092
references.citation: Cell Physiol Biochem. 2001;11(4):209-18
references.pmid: 11509829
references.citation: Trends Neurosci. 2003 Apr;26(4):184-92
references.pmid: 12689769
references.citation: Annu Rev Neurosci. 2006;29:565-98
references.pmid: 16776597
references.citation: Neuron. 2005 Oct 20;48(2):303-14
references.pmid: 16242410
references.citation: Proc Natl Acad Sci U S A. 1988 Jul;85(14):5274-8
references.pmid: 2899326
references.citation: Neuron. 2009 Jan 15;61(1):85-100
references.pmid: 19146815
references.citation: Ann N Y Acad Sci. 2004 Jun;1018:192-8
references.pmid: 15240368
references.citation: J Neurochem. 2008 Jul;106(2):805-14
references.pmid: 18489715
references.citation: Cell. 1990 Sep 21;62(6):1205-15
references.pmid: 2169352
references.citation: Nature. 2007 Apr 26;446(7139):1086-90
references.pmid: 17460674
references.citation: J Neurosci. 2008 Jan 2;28(1):264-78
references.pmid: 18171944
references.citation: J Neurosci. 2000 Dec 1;20(23):8701-9
references.pmid: 11102476
references.citation: Nat Neurosci. 2004 Jun;7(6):583-4
references.pmid: 15146188
references.citation: J Neurochem. 2004 Oct;91(1):38-48
references.pmid: 15379885
references.citation: FASEB J. 2008 Aug;22(8):2872-9
references.pmid: 18424767
references.citation: Neuropsychopharmacology. 2009 Dec;34(13):2642-54
references.pmid: 19727068
references.citation: J Neurochem. 2004 Jan;88(2):380-93
references.pmid: 14690526
references.citation: Nat Neurosci. 2006 Apr;9(4):475-7
references.pmid: 16520736
references.citation: Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5764-8
references.pmid: 1631058
references.citation: Brain Res. 2007 Jul 23;1159:141-7
references.pmid: 17574218
references.citation: Curr Opin Pharmacol. 2005 Feb;5(1):26-33
references.pmid: 15661622
references.citation: J Pharmacol Exp Ther. 1966 Jul;153(1):121-7
references.pmid: 4288396
references.citation: PLoS Genet. 2009 May;5(5):e1000489
references.pmid: 19461886
references.citation: Science. 1991 Oct 25;254(5031):576-8
references.pmid: 1948034
references.citation: FASEB J. 2010 Jul;24(7):2427-35
references.pmid: 20223941
references.citation: J Neurosci. 2005 Jun 22;25(25):6005-15
references.pmid: 15976090
references.citation: Brain Res. 2009 Aug 25;1286:1-12
references.pmid: 19545546
references.citation: Neurochem Res. 2004 Feb;29(2):357-69
references.pmid: 15002731
references.citation: Physiol Genomics. 2003 Aug 15;14(3):251-60
references.pmid: 12824457
references.citation: Science. 1994 Aug 19;265(5175):1104-7
references.pmid: 8066450
references.citation: PLoS One. 2009 Jun 30;4(6):e6092
references.pmid: 19564919
references.citation: Evolution. 1989 Jan;43(1):223-225
references.pmid: 28568501
references.citation: Curr Opin Neurobiol. 2005 Oct;15(5):599-606
references.pmid: 16150584
references.citation: Neuropharmacology. 2006 Aug;51(2):367-73
references.pmid: 16777145
references.citation: Proc Natl Acad Sci U S A. 1976 Oct;73(10):3729-33
references.pmid: 185626
references.citation: Synapse. 2002 Sep 15;45(4):220-9
references.pmid: 12125043
references.citation: J Lipid Res. 2002 Nov;43(11):1770-2
references.pmid: 12401877
references.citation: Genome Biol. 2004;5(10):R80
references.pmid: 15461798
references.citation: Pharmacopsychiatry. 2009 May;42 Suppl 1:S42-55
references.pmid: 19434555
references.citation: Gene. 1989 Aug 15;80(2):325-36
references.pmid: 2511075
references.citation: Eur J Neurosci. 2002 Aug;16(3):387-94
references.pmid: 12193179
references.citation: Neuroscience. 2005;136(4):1121-32
references.pmid: 16216424
references.citation: Psychopharmacology (Berl). 2009 Dec;207(2):245-55
references.pmid: 19787337
references.citation: Science. 1991 Oct 25;254(5031):578-9
references.pmid: 1948035
references.citation: J Psychiatry Neurosci. 2000 Mar;25(2):125-36
references.pmid: 10740986
references.citation: Neuron. 2006 Nov 9;52(3):461-74
references.pmid: 17088212
references.citation: J Pharmacol Exp Ther. 1998 Oct;287(1):72-80
references.pmid: 9765324
references.citation: Synapse. 1994 Oct;18(2):161-7
references.pmid: 7839314
references.citation: Drug Metab Dispos. 2010 Jan;38(1):157-67
references.pmid: 19786507
references.citation: Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7742-7
references.pmid: 9636221
references.citation: Neuropsychopharmacology. 2001 Feb;24(2):97-129
references.pmid: 11120394
references.citation: J Neurosci. 2005 Dec 7;25(49):11300-12
references.pmid: 16339025
references.citation: BMC Bioinformatics. 2005 Nov 09;6:269
references.pmid: 16280084
references.citation: Nature. 1993 Sep 23;365(6444):314-20
references.pmid: 8397338
references.citation: Trends Neurosci. 2005 Aug;28(8):436-45
references.pmid: 15982754
references.citation: Eur Neuropsychopharmacol. 2003 Dec;13(6):435-41
references.pmid: 14636959
references.citation: Biol Psychiatry. 2007 Jan 1;61(1):78-86
references.pmid: 16876134
references.citation: Neuron. 2006 Nov 9;52(3):445-59
references.pmid: 17088211
references.citation: Proc Natl Acad Sci U S A. 1990 Sep;87(17):6912-6
references.pmid: 2118661
references.citation: J Neurosci. 2005 Jul 27;25(30):7048-53
references.pmid: 16049181
references.citation: Eur J Neurosci. 2005 Aug;22(4):939-48
references.pmid: 16115217
references.citation: Neurochem Res. 1998 May;23(5):645-52
references.pmid: 9566602
references.citation: Br J Pharmacol Chemother. 1955 Jun;10(2):260-4
references.pmid: 14389670
references.citation: Nat Neurosci. 2005 Jun;8(6):759-67
references.pmid: 15880109
references.citation: Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):31-6
references.pmid: 11134512
references.citation: Nat Rev Neurosci. 2007 Nov;8(11):844-58
references.pmid: 17948030
references.citation: Genome Biol. 2009;10(5):R55
references.pmid: 19463160
references.citation: Neuropsychopharmacology. 2005 Sep;30(9):1751-63
references.pmid: 15870834
references.citation: PLoS Genet. 2008 Nov;4(11):e1000287
references.pmid: 19043577
references.citation: Genome Biol. 2007;8(9):R183
references.pmid: 17784955
references.citation: Neurosci Lett. 2000 Jul 7;288(1):76-80
references.pmid: 10869819
references.citation: J Neurosci. 1995 Jan;15(1 Pt 2):721-30
references.pmid: 7823175
references.citation: Nature. 2001 May 31;411(6837):583-7
references.pmid: 11385572
references.citation: Science. 2002 Apr 19;296(5567):550-3
references.pmid: 11910072
references.citation: Ann N Y Acad Sci. 2006 Aug;1074:295-302
references.pmid: 17105925
references.citation: Trends Pharmacol Sci. 1998 Feb;19(2):67-74
references.pmid: 9550944
references.citation: Nature. 2008 Oct 30;455(7217):1198-204
references.pmid: 18815592
references.citation: Cell. 2004 Dec 29;119(7):1041-54
references.pmid: 15620361
references.citation: Behav Brain Res. 1999 Jun;101(2):129-52
references.pmid: 10372570
references.citation: Trends Neurosci. 2007 Aug;30(8):399-406
references.pmid: 17629579
references.citation: J Neurosci. 1992 Feb;12(2):483-8
references.pmid: 1346804
references.citation: Science. 2006 Sep 29;313(5795):1929-35
references.pmid: 17008526
references.citation: J Neurosci. 2005 Mar 2;25(9):2255-66
references.pmid: 15745951