title: Attenuation of ecstasy-induced neurotoxicity by N-acetylcysteine.
abstract: Exposure to 3, 4-methylenedioxymethamphetamine (MDMA) can lead to spatial memory impairments and hippocampal cell death. Numerous evidence indicates that the antioxidant N-acetylcysteine (NAC) exerts protective effects in the brain. The present study evaluates the effects of NAC on MDMA-induced neurotoxicity.
  
  
  METHODS
  We intraperitoneally injected 28 adult male Sprague-Dawley rats (200-250 g) with either 0, 10 mg/kg of MDMA, or 10 mg/kg of MDMA plus 100 mg/kg of NAC. Spatial memory was assessed with a Morris Water Maze (MWM). At the end of the study, rats' brains were removed to study the structure and ultrastructure of CA1, and measure Bcl-2 and Bax expressions in the hippocampus. In the MWM, NAC treatment significantly attenuated the MDMA-induced increase in distance traveled (p < 0.05) and escape latency (p < 0.001). The decreased time spent in the target quadrant in MDMA-treated animals was attenuated by NAC (p < 0.01). NAC significantly protected against MDMA-induced apoptosis and the up- and down-regulation of Bax and Bcl-2, respectively. These data have suggested that NAC could protect against behavioral changes and apoptosis in the hippocampus following administration of MDMA. NAC might be useful for the treatment of neurotoxicity in MDMA users.
authors.affiliation: Research Center for Behavioral Disorders and Substance Abuse, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Soleimani Asl
authors.forename: Bita
authors.initials: B
authors.lastname: Saifi
authors.forename: Abolhasan
authors.initials: A
authors.lastname: Sakhaie
authors.forename: Somayeh
authors.initials: S
authors.lastname: Zargooshnia
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mehdizadeh
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D007859:Learning Disabilities / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000975:Antioxidants; C494828:Bax protein, rat; D009419:Nerve Tissue Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D000111:Acetylcysteine
references.citation: Toxicol Lett. 2013 Apr 26;218(3):299-307
references.pmid: 23296100
references.citation: Mol Neurobiol. 2009 Jun;39(3):210-71
references.pmid: 19373443
references.citation: J Psychopharmacol. 1998;12(1):79-83
references.pmid: 9584971
references.citation: Free Radic Biol Med. 1999 Jul;27(1-2):28-33
references.pmid: 10443916
references.citation: Int J Dev Neurosci. 2004 Aug-Oct;22(5-6):261-71
references.pmid: 15380826
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2008 May 15;32(4):1064-8
references.pmid: 18403082
references.citation: Brain Res Bull. 1995;38(5):425-34
references.pmid: 8665265
references.citation: Cell J. 2012 Fall;14(3):177-84
references.pmid: 23508562
references.citation: Int J Neuropsychopharmacol. 2013 Sep;16(8):1849-65
references.pmid: 23590859
references.citation: J Neurosci Res. 2010 Mar;88(4):905-16
references.pmid: 19798748
references.citation: Neurochem Res. 2006 Apr;31(4):473-81
references.pmid: 16758355
references.citation: Cerebellum. 2007;6(4):308-14
references.pmid: 17853088
references.citation: J Autoimmune Dis. 2005 May 03;2(1):4
references.pmid: 15869713
references.citation: Pharmacol Biochem Behav. 2000 Jul;66(3):501-8
references.pmid: 10899362
references.citation: FASEB J. 2004 Feb;18(2):238-51
references.pmid: 14769818
references.citation: Brain Res. 2003 Jun 6;974(1-2):127-33
references.pmid: 12742630
references.citation: Toxicol Appl Pharmacol. 2008 Jul 1;230(1):117-25
references.pmid: 18358511
references.citation: FASEB J. 1997 Feb;11(2):141-6
references.pmid: 9039956
references.citation: Curr Opin Pharmacol. 2007 Aug;7(4):355-9
references.pmid: 17602868
references.citation: Brain. 2003 Dec;126(Pt 12):2738-49
references.pmid: 14506071
references.citation: Drug Metab Lett. 2008 Apr;2(2):95-9
references.pmid: 19356078
references.citation: Hum Psychopharmacol. 2001 Dec;16(8):619-625
references.pmid: 12404542
references.citation: Brain Res. 2003 May 2;971(1):1-8
references.pmid: 12691831
references.citation: J Pharmacol Exp Ther. 2001 Jun;297(3):846-52
references.pmid: 11356903
references.citation: Toxicol Appl Pharmacol. 2004 Apr 15;196(2):223-34
references.pmid: 15081269
references.citation: Curr Neuropharmacol. 2011 Mar;9(1):84-90
references.pmid: 21886568
references.citation: Brain Res Bull. 2000 Apr;51(6):499-505
references.pmid: 10758340
references.citation: Eur J Pharmacol. 2010 Sep 25;643(2-3):162-9
references.pmid: 20599925
references.citation: Psychopharmacology (Berl). 1995 Jun;119(3):247-60
references.pmid: 7675958
references.citation: CNS Drugs. 2014 Feb;28(2):95-106
references.pmid: 24442756
references.citation: Psychopharmacology (Berl). 2000 Feb;148(3):322-4
references.pmid: 10755746
references.citation: Neuroreport. 2010 Apr 21;21(6):416-21
references.pmid: 20838280
references.citation: Clin Exp Dermatol. 2013 Jun;38(4):403-9
references.pmid: 23517443
references.citation: Psychol Med. 2001 May;31(4):647-58
references.pmid: 11352367
references.citation: J Pharmacol Exp Ther. 2005 Apr;313(1):422-31
references.pmid: 15634943
references.citation: Biomaterials. 2005 Sep;26(26):5321-9
references.pmid: 15814130
references.citation: Chem Res Toxicol. 1988 Nov-Dec;1(6):370-8
references.pmid: 2908769
references.citation: Physiol Behav. 2003 Jul;79(2):281-7
references.pmid: 12834800
references.citation: Brain Res Brain Res Rev. 2003 May;42(2):155-68
references.pmid: 12738056
references.citation: J Neuroimmune Pharmacol. 2008 Dec;3(4):203-17
references.pmid: 18709468
references.citation: J Neurochem. 2001 Jan;76(1):224-33
references.pmid: 11145996
references.citation: Basic Clin Pharmacol Toxicol. 2009 Aug;105(2):98-104
references.pmid: 19389043
references.citation: J Comp Neurol. 2006 Jul 10;497(2):251-69
references.pmid: 16705678
references.citation: Pharmacol Rep. 2009 Sep-Oct;61(5):941-6
references.pmid: 19904020
references.citation: Biol Psychiatry. 2001 Oct 1;50(7):550-4
references.pmid: 11600108
references.citation: Neurol Res. 2007 Apr;29(3):239-42
references.pmid: 17509221
references.citation: Metab Brain Dis. 2013 Dec;28(4):677-86
references.pmid: 23975535
references.citation: Funct Neurol. 2015 Apr-Jun;30(2):131-7
references.pmid: 26415786
references.citation: Free Radic Biol Med. 2012 Sep 15;53(6):1252-63
references.pmid: 22841758
references.citation: Brain Res. 2004 Jul 30;1016(1):90-5
references.pmid: 15234256
references.citation: Biomaterials. 2006 Mar;27(9):1803-9
references.pmid: 16289659
references.citation: Eur J Clin Invest. 2002 May;32(5):360-71
references.pmid: 12027877
references.citation: Cell J. 2012 Winter;13(4):275-80
references.pmid: 23508090
references.citation: Sichuan Da Xue Xue Bao Yi Xue Ban. 2009 Nov;40(6):1000-2, 1037
references.pmid: 20067106
references.citation: Neurotoxicology. 1998 Jun;19(3):427-41
references.pmid: 9621349
references.citation: Neuropsychopharmacology. 1988 Dec;1(4):273-7
references.pmid: 2908020
references.citation: Biochim Biophys Acta. 2013 Aug;1830(8):4117-29
references.pmid: 23618697