title: CREB involvement in the regulation of striatal prodynorphin by nicotine.
abstract: BACKGROUND
  The transcription factor cAMP response element binding (CREB) protein plays a pivotal role in drug-dependent neuronal plasticity. CREB phosphorylation at Ser133 is enhanced by drugs of abuse, including nicotine. Dynorphin (Dyn) contributes to the addictive process and its precursor gene prodynorphin (PD) is regulated by CREB. PD mRNA and Dyn synthesis were enhanced in the striatum following acute nicotine, suggesting genomic regulation.
  
  
  OBJECTIVE
  These studies investigated PD transcription in mice acutely treated with nicotine, determined the role of CREB, and characterized the receptors involved.
  
  
  RESULTS
  Acute nicotine increased adenylyl cyclase activity, cAMP, and pCREB Ser133 levels in striatum and enhanced CREB binding to CRE elements (DynCREs) of the PD promoter, preferentially DynCRE3. DynCRE3 binding was dose dependent with 1 mg of nicotine giving a maximal response. Additionally, DynCRE binding was time dependent, rising by 15 min, reaching a maximum at 1 h, and returning to control by 3 h, a temporal pattern similar to that of cAMP and pCREB. Supershift experiments showed that CREB and pCREB Ser133 were the major contributors to DynCRE3 binding complex. The nAChR antagonist mecamylamine and the dopamine D1-like receptor antagonist SCH 23390 prevented the nicotine-induced increase of pCREB and nuclear protein binding to DynCRE3.
  
  
  CONCLUSIONS
  Our findings suggest that nicotine regulates PD expression in striatum at the transcriptional level and CREB is involved. Dopamine D1 receptor stimulation by nAChR-released dopamine appears to be an underlying mechanism. Altered Dyn synthesis might be relevant for the behavioral actions of nicotine and especially its aversive properties.
authors.affiliation: Department of Psychiatry, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McCarthy
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Duchemin
authors.forename: Norton H
authors.initials: NH
authors.lastname: Neff
authors.forename: Maria
authors.initials: M
authors.lastname: Hadjiconstantinou
mesh_terms: D000262:Adenylyl Cyclases / Q000096:biosynthesis; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000378:metabolism; D004745:Enkephalins / Q000096:biosynthesis*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010766:Phosphorylation; D011485:Protein Binding / Q000187:drug effects; D011498:Protein Precursors / Q000096:biosynthesis*; D020218:Response Elements / Q000187:drug effects; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D001552:Benzazepines; C116472:Creb3 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004745:Enkephalins; D011498:Protein Precursors; C534628:SCH 23390; D008464:Mecamylamine; D009538:Nicotine; D004399:Dynorphins; C033660:preproenkephalin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases
references.citation: Pharmacol Ther. 2004 Oct;104(1):47-58
references.pmid: 15500908
references.citation: Brain Res Brain Res Rev. 1994 Jan;19(1):1-28
references.pmid: 7909470
references.citation: Nat Rev Mol Cell Biol. 2001 Aug;2(8):599-609
references.pmid: 11483993
references.citation: J Neurosci Res. 2004 Sep 15;77(6):884-91
references.pmid: 15334606
references.citation: J Neurosci. 1999 Sep 15;19(18):8145-51
references.pmid: 10479714
references.citation: Neuropharmacology. 2002 Mar;42(4):530-9
references.pmid: 11955523
references.citation: Mol Cell Biol. 1993 Aug;13(8):4852-9
references.pmid: 8336722
references.citation: Neuropsychopharmacology. 2009 Jul;34(8):1993-2001
references.pmid: 19212318
references.citation: Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14928-33
references.pmid: 8962158
references.citation: Psychopharmacology (Berl). 1985;86(3):274-80
references.pmid: 2994144
references.citation: Psychopharmacology (Berl). 1989;98(2):203-6
references.pmid: 2569217
references.citation: Neuropharmacology. 2000 Oct;39(13):2840-7
references.pmid: 11044754
references.citation: J Neurosci. 2011 Feb 23;31(8):3095-103
references.pmid: 21414930
references.citation: Drug Alcohol Depend. 1997 Mar 14;44(2-3):105-15
references.pmid: 9088782
references.citation: Annu Rev Neurosci. 2011;34:441-66
references.pmid: 21469956
references.citation: Ann N Y Acad Sci. 2007 May;1104:192-212
references.pmid: 17416920
references.citation: Brain Res Mol Brain Res. 1996 Aug;40(1):15-21
references.pmid: 8840008
references.citation: Cell. 1994 Nov 18;79(4):729-42
references.pmid: 7954836
references.citation: Neuron. 1991 Apr;6(4):607-17
references.pmid: 1901718
references.citation: J Neurochem. 2008 Mar;104(6):1440-9
references.pmid: 18221378
references.citation: J Neurochem. 2001 May;77(3):943-52
references.pmid: 11331423
references.citation: Science. 1998 Dec 18;282(5397):2272-5
references.pmid: 9856954
references.citation: J Pharmacol Exp Ther. 1993 Oct;267(1):145-52
references.pmid: 7901389
references.citation: Pharmacol Biochem Behav. 1985 Feb;22(2):237-41
references.pmid: 2858867
references.citation: Neurosci Lett. 2009 Dec 25;467(2):182-6
references.pmid: 19835933
references.citation: Neuroreport. 1994 Jun 2;5(10):1213-6
references.pmid: 7919167
references.citation: Psychopharmacology (Berl). 2009 Jan;201(4):507-16
references.pmid: 18807250
references.citation: J Neurosci. 2001 Dec 1;21(23):9438-44
references.pmid: 11717377
references.citation: Curr Neuropharmacol. 2007 Sep;5(3):202-12
references.pmid: 19305803
references.citation: J Neurosci. 2009 Feb 11;29(6):1855-9
references.pmid: 19211892
references.citation: Mol Endocrinol. 1994 Mar;8(3):333-44
references.pmid: 8015551
references.citation: J Pharmacol Exp Ther. 2007 Jul;322(1):23-9
references.pmid: 17468300
references.citation: Mol Cell Biol. 1994 May;14(5):2837-48
references.pmid: 8164647
references.citation: Neuropsychopharmacology. 1997 Sep;17(3):151-61
references.pmid: 9272482
references.citation: Neuron. 1995 Apr;14(4):813-23
references.pmid: 7718243
references.citation: Brain Res. 1996 Aug 19;730(1-2):133-42
references.pmid: 8883897
references.citation: J Neurochem. 2003 Mar;84(6):1431-41
references.pmid: 12614343
references.citation: Pharmacol Biochem Behav. 1995 Jun-Jul;51(2-3):457-61
references.pmid: 7667368
references.citation: Neurosci Lett. 2011 Mar 17;491(2):108-12
references.pmid: 21232579
references.citation: Psychopharmacology (Berl). 2009 Nov;207(1):57-71
references.pmid: 19711055
references.citation: J Pharmacol Exp Ther. 2009 Aug;330(2):541-9
references.pmid: 19435931
references.citation: J Pharmacol Exp Ther. 2006 Jan;316(1):440-7
references.pmid: 16223871
references.citation: J Neurochem. 1998 Mar;70(3):914-21
references.pmid: 9489710
references.citation: Psychopharmacology (Berl). 2004 Apr;172(4):463-70
references.pmid: 14727002
references.citation: J Neurosci. 2001 Sep 15;21(18):7397-403
references.pmid: 11549750
references.citation: Brain Res. 2007 Oct 31;1178:12-9
references.pmid: 17920048
references.citation: Neurosci Biobehav Rev. 1998 Mar;22(2):335-45
references.pmid: 9579323
references.citation: Synapse. 1995 Mar;19(3):151-9
references.pmid: 7784955
references.citation: Exp Brain Res. 1998 Nov;123(1-2):60-76
references.pmid: 9835393
references.citation: Annu Rev Biochem. 1999;68:821-61
references.pmid: 10872467
references.citation: Brain Res Mol Brain Res. 1994 Apr;23(1-2):1-13
references.pmid: 7913201
references.citation: J Neurochem. 2003 Jul;86(2):451-9
references.pmid: 12871586
references.citation: J Neurosci. 2002 Dec 15;22(24):10883-90
references.pmid: 12486182
references.citation: Pharmacol Biochem Behav. 2005 Dec;82(4):751-7
references.pmid: 16412500
references.citation: J Neurosci. 2004 Mar 31;24(13):3344-54
references.pmid: 15056714
references.citation: Neuropharmacology. 2004;47 Suppl 1:24-32
references.pmid: 15464123
references.citation: Trends Neurosci. 2005 Aug;28(8):436-45
references.pmid: 15982754
references.citation: J Neurosci. 2001 Dec 15;21(24):9930-43
references.pmid: 11739600
references.citation: J Neurosci. 2005 Dec 7;25(49):11444-54
references.pmid: 16339038
references.citation: Curr Mol Med. 2002 Nov;2(7):649-65
references.pmid: 12420804
references.citation: Psychopharmacology (Berl). 2010 Jun;210(2):121-35
references.pmid: 20352414
references.citation: Neuroscience. 1995 Apr;65(4):1051-61
references.pmid: 7617161
references.citation: Mol Cell Neurosci. 1994 Jun;5(3):238-45
references.pmid: 8087422
references.citation: Brain Res Rev. 2009 Dec 11;62(1):127-46
references.pmid: 19804796
references.citation: Brain Res Mol Brain Res. 1998 Jan;53(1-2):260-9
references.pmid: 9473689
references.citation: J Pharmacol Exp Ther. 1993 Jan;264(1):489-95
references.pmid: 8093731
references.citation: Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9631-5
references.pmid: 7937819
references.citation: Neuron. 2005 Jun 16;46(6):933-43
references.pmid: 15953421
references.citation: Biochem Pharmacol. 2009 Oct 1;78(7):744-55
references.pmid: 19523928
references.citation: Psychopharmacology (Berl). 2000 Oct;152(3):321-33
references.pmid: 11105943
references.citation: Psychopharmacology (Berl). 2010 Jun;210(2):221-9
references.pmid: 19806344
references.citation: Science. 1986 Aug 15;233(4765):774-6
references.pmid: 3016896