The Brain-Specific Neural Zinc Finger Transcription Factor 2b (NZF-2b/7ZFMyt1) Suppresses Cocaine Self-Administration in Rats.
Brain-specific neural-zinc-finger transcription factor-2b (NZF2b/7ZFMyt1) is induced in the mesolimbic dopaminergic region after chronic cocaine exposure and lentiviral-mediated expression of NZF2b/7ZFMyt1 in the nucleus accumbens results in decreased locomotor activity (Chandrasekar and Dreyer, 2010). In this study the role of NZF2b/7ZFMyt1 in active cocaine seeking and of its interaction with histone deacetylase on the altered behavior has been observed. Localized expression of NZF2b/7ZFMyt1 in the nucleus accumbens resulted in attenuated cocaine self-administration, whereas silencing this transcription factor with lentiviruses expressing siRNAs increased the animal's motivation to self-infuse cocaine. Low doses of sodium butyrate, a potent inhibitor of histone deacetylase, were sufficient to reverse the NZF2b/7ZFMyt1-mediated decrease in cocaine self-administration. NZF2b/7ZFMyt1 expression resulted in strong induction of transcription factors REST1 and NAC1 and of the dopamine D2 receptor, with concomitant inhibition of BDNF and its receptor TrkB. We show that NZF2b/7ZFMyt1 colocalizes with histone deacetylase-2 (HDAC2), probably overcoming the suppression of transcriptional activity caused by Lingo1. These findings show that molecular adaptations mediated by NZF2b/7ZFMyt1 expression possibly lead to decreased responsiveness to the reinforcing properties of cocaine and play a prominent role in affecting the behavioral changes induced by the drug.
Chandrasekar
Vijay
V
Division of Biochemistry, Department of Medicine, University of Fribourg Fribourg, Switzerland.
Dreyer
Jean-Luc
JL
J Neurosci Res. 1997 Oct 15;50(2):272-90
9373037
Am J Physiol Gastrointest Liver Physiol. 2004 Jun;286(6):G1000-8
14726307
Br J Pharmacol. 2008 May;154(2):327-42
18345022
J Neurosci. 2002 Apr 1;22(7):2977-88
11923462
Mol Cell Neurosci. 2004 Jan;25(1):111-23
14962745
Brain Res. 2006 Feb 3;1071(1):218-25
16423334
J Psychopharmacol. 1998;12(1):54-67
9584969
Neuron. 2000 Mar;25(3):515-32
10774721
Neuroscience. 2002;110(3):421-9
11906783
Biochem Biophys Res Commun. 2009 Jul 10;384(4):506-11
19426709
J Neurosci. 2002 Oct 1;22(19):8347-51
12351707
J Biol Chem. 2004 Jan 2;279(1):556-61
14561745
Curr Opin Pharmacol. 2009 Feb;9(1):53-8
19138563
Neuron. 2004 Jun 24;42(6):947-59
15207239
J Neurochem. 2005 Mar;92(5):1243-55
15715673
Neurosci Lett. 2008 Aug 15;441(1):72-6
18599214
Eur J Neurosci. 2007 Nov;26(10):2764-76
18001274
Mol Cell Biol. 1992 Dec;12(12):5632-9
1280325
J Neurosci. 1997 Nov 1;17(21):8147-55
9334390
Cereb Cortex. 2000 Mar;10(3):318-25
10731226
Nat Genet. 2000 Nov;26(3):277-81
11062465
J Neurochem. 2005 Jun;93(6):1444-53
15935060
Neurochem Int. 2009 Mar-Apr;54(3-4):245-52
19121354
Nat Neurosci. 2007 Aug;10(8):1029-37
17618281
Philos Trans R Soc Lond B Biol Sci. 2003 Apr 29;358(1432):815-9
12740128
Science. 2008 Sep 19;321(5896):1690-2
18802002
Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19186-91
16380431
J Neurochem. 2004 Sep;90(5):1117-31
15312167
Pharmacol Biochem Behav. 2003 Apr;75(1):49-54
12759112
Glia. 1995 Aug;14(4):303-21
8530187
Neuron. 2004 Jun 24;42(6):961-72
15207240
Neuron. 2005 Oct 20;48(2):303-14
16242410
J Neurosci. 1997 Apr 1;17(7):2295-313
9065491
Nat Neurosci. 2008 Jul;11(7):737-8
18575469
Eur J Neurosci. 2005 Jul;22(2):397-403
16045493
Am J Addict. 2001 Summer;10(3):201-17
11579619
Neuroreport. 2004 Oct 25;15(15):2397-400
15640763
Eur J Neurosci. 2004 Mar;19(6):1621-33
15066158
J Neurosci. 2000 Aug 15;20(16):6210-7
10934270
Epigenetics. 2007 Oct-Dec;2(4):214-22
18075316
Cell. 2002 Nov 15;111(4):483-93
12437922
Stem Cells. 2007 Feb;25(2):354-63
17082226
Dev Neurobiol. 2008 Mar;68(4):521-41
18186492
Nat Rev Neurosci. 2007 May;8(5):355-67
17453016
EMBO J. 1990 Aug;9(8):2459-64
2369898
Psychopharmacology (Berl). 2008 Aug;199(2):169-82
18551281
J Biol Chem. 2004 Sep 24;279(39):40545-59
15273246
Behav Brain Res. 2007 Jul 19;181(1):76-84
17477979
J Neurosci. 2007 Jul 4;27(27):7117-24
17611264
J Neurochem. 2007 May;101(3):611-8
17254023
Mol Cell Neurosci. 2005 Feb;28(2):275-91
15691709
J Neurochem. 2005 Aug;94(3):786-93
16033423
Neuropsychopharmacology. 2008 Jan;33(1):166-80
17805308
Brain Res. 2006 Jan 5;1067(1):1-12
16376315
Cell. 1996 Dec 27;87(7):1191-202
8980226
Neuroscience. 1995 Jan;64(1):71-80
7708216
Neuron. 2007 Nov 8;56(3):517-29
17988634
Mech Dev. 2002 Oct;118(1-2):209-13
12351189
Nature. 2008 Jul 3;454(7200):118-21
18500330
Nature. 1997 Oct 23;389(6653):856-60
9349818
J Neurosci. 2002 May 1;22(9):3312-20
11978805
J Neurosci. 2003 Oct 15;23(28):9418-27
14561870
J Neurosci. 2005 Dec 7;25(49):11444-54
16339038
Nat Neurosci. 2007 Aug;10(8):935-6
17657232
J Neurosci. 2004 Jun 16;24(24):5603-10
15201333
J Neurosci. 2003 Feb 1;23(3):742-7
12574402
Neurobiol Dis. 2010 Jan;37(1):86-98
19786102