title: Altered learning and Arc-regulated consolidation of learning in striatum by methamphetamine-induced neurotoxicity.
abstract: Methamphetamine (METH) causes partial depletion of central monoamine systems and cognitive dysfunction in rats and humans. We have previously shown and now further show that the positive correlation between expression of the immediate-early gene Arc (activity-regulated, cytoskeleton-associated) in the dorsomedial (DM) striatum and learning on a response reversal task is lost in rats with METH-induced striatal dopamine loss, despite normal behavioral performance and unaltered N-methyl-D-aspartate (NMDA) receptor-mediated excitatory post-synaptic currents, suggesting intact excitatory transmission. This discrepancy suggests that METH-pretreated rats may no longer be using the dorsal striatum to solve the reversal task. To test this hypothesis, male Sprague-Dawley rats were pretreated with a neurotoxic regimen of METH or saline. Guide cannulae were surgically implanted bilaterally into the DM striatum. Three weeks after METH treatment, rats were trained on a motor response version of a T-maze task, and then underwent reversal training. Before reversal training, the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5) or an Arc antisense oligonucleotide was infused into the DM striatum. Acute disruption of DM striatal function by infusion of AP5 impaired reversal learning in saline-, but not METH-, pretreated rats. Likewise, acute disruption of Arc, which is implicated in consolidation of long-term memory, disrupted retention of reversal learning 24 h later in saline-, but not METH-, pretreated rats. These results highlight the critical importance of Arc in the striatum in consolidation of basal ganglia-mediated learning and suggest that long-term toxicity induced by METH alters the cognitive strategies/neural circuits used to solve tasks normally mediated by dorsal striatal function.
authors.affiliation: Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Elissa D
authors.initials: ED
authors.lastname: Pastuzyn
authors.forename: David E
authors.initials: DE
authors.lastname: Chapman
authors.forename: Karen S
authors.initials: KS
authors.lastname: Wilcox
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Keefe
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage; D019969:Amphetamine-Related Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D017781:Genes, Immediate-Early / Q000187:drug effects / Q000235:genetics; D007859:Learning Disabilities / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009498:Neurotoxins / Q000008:administration & dosage; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018759:Adrenergic Uptake Inhibitors; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; C092069:activity regulated cytoskeletal-associated protein; D008694:Methamphetamine
references.citation: J Comp Neurol. 2006 Sep 20;498(3):317-29
references.pmid: 16871537
references.citation: Pharmacol Rev. 1999 Mar;51(1):7-61
references.pmid: 10049997
references.citation: Neurobiol Learn Mem. 2003 Nov;80(3):257-67
references.pmid: 14521868
references.citation: Brain Res. 1980 Jan 6;181(1):151-60
references.pmid: 7350950
references.citation: J Neurophysiol. 2003 Jan;89(1):69-80
references.pmid: 12522160
references.citation: Neuropsychopharmacology. 2010 Jan;35(2):505-14
references.pmid: 19794407
references.citation: Arch Gen Psychiatry. 2006 Jan;63(1):90-100
references.pmid: 16389202
references.citation: Eur J Pharmacol. 2009 Apr 1;607(1-3):68-73
references.pmid: 19326567
references.citation: Neurotox Res. 2008 Dec;14(4):307-15
references.pmid: 19073434
references.citation: J Pharmacol Exp Ther. 2001 Feb;296(2):520-7
references.pmid: 11160639
references.citation: Nature. 1994 Oct 20;371(6499):704-7
references.pmid: 7935816
references.citation: J Neurosci. 1998 Oct 15;18(20):8417-22
references.pmid: 9763484
references.citation: Neuropsychopharmacology. 2005 Jun;30(6):1128-37
references.pmid: 15688084
references.citation: Biol Psychiatry. 2011 Apr 1;69(7):704-7
references.pmid: 21074144
references.citation: Cereb Cortex. 1998 Oct-Nov;8(7):602-13
references.pmid: 9823481
references.citation: Synapse. 1992 Sep;12(1):27-36
references.pmid: 1411961
references.citation: J Neurosci. 2001 Jul 15;21(14):5089-98
references.pmid: 11438584
references.citation: J Neurosci. 2001 Dec 1;21(23):9414-8
references.pmid: 11717374
references.citation: Behav Neurosci. 2004 Apr;118(2):438-42
references.pmid: 15113271
references.citation: Annu Rev Neurosci. 2009;32:267-87
references.pmid: 19555290
references.citation: J Neurosci. 2005 Jan 12;25(2):532-8
references.pmid: 15647499
references.citation: Psychopharmacology (Berl). 2008 Sep;199(4):637-50
references.pmid: 18509623
references.citation: Brain Res. 1992 Dec 11;598(1-2):321-6
references.pmid: 1486494
references.citation: Nat Neurosci. 2005 Jun;8(6):805-12
references.pmid: 15908948
references.citation: Brain Struct Funct. 2010 Jul;215(1):1-28
references.pmid: 20390296
references.citation: J Pharmacol Exp Ther. 1980 Aug;214(2):257-62
references.pmid: 6104722
references.citation: Neurobiol Learn Mem. 2004 Sep;82(2):81-9
references.pmid: 15341793
references.citation: Int J Neuropsychopharmacol. 2011 Jul;14(6):784-95
references.pmid: 20942997
references.citation: J Neurosci. 2000 Jun 1;20(11):4320-4
references.pmid: 10818167
references.citation: J Neurosci. 1994 Sep;14(9):5471-84
references.pmid: 7916045
references.citation: Synapse. 1998 Nov;30(3):329-33
references.pmid: 9776136
references.citation: Behav Brain Res. 2011 Jan 1;216(1):396-401
references.pmid: 20797410
references.citation: Nat Med. 1996 Jun;2(6):699-703
references.pmid: 8640565
references.citation: Psychopharmacology (Berl). 2009 Mar;202(4):649-61
references.pmid: 18841348
references.citation: Neurosci Lett. 2008 Feb 13;432(1):40-5
references.pmid: 18248891
references.citation: Neuroscience. 2006 Sep 29;142(1):1-20
references.pmid: 16887277
references.citation: J Physiol. 1998 Feb 15;507 ( Pt 1):13-24
references.pmid: 9490809
references.citation: Brain Res Brain Res Rev. 2002 Sep;39(2-3):107-40
references.pmid: 12423763
references.citation: Neuropsychopharmacology. 2009 Jul;34(8):2041-52
references.pmid: 19262467
references.citation: Pharmacol Rev. 2010 Sep;62(3):405-96
references.pmid: 20716669
references.citation: Brain Res Mol Brain Res. 1999 Jan 22;64(1):11-23
references.pmid: 9889300
references.citation: J Neurosci. 2011 Mar 16;31(11):4290-7
references.pmid: 21411670
references.citation: Am J Psychiatry. 2001 Mar;158(3):377-82
references.pmid: 11229977
references.citation: J Neurochem. 1999 Feb;72(2):661-8
references.pmid: 9930738
references.citation: Brain Res. 2002 Oct 25;953(1-2):205-14
references.pmid: 12384254
references.citation: Neuropharmacology. 1980 Oct;19(10):989-95
references.pmid: 6106905
references.citation: J Neurophysiol. 1996 Nov;76(5):3415-24
references.pmid: 8930282
references.citation: Cereb Cortex. 2007 Jan;17(1):18-27
references.pmid: 16481566
references.citation: Drug Alcohol Depend. 1976 Feb;1(3):215-9
references.pmid: 828106
references.citation: Synapse. 1996 Aug;23(4):328-34
references.pmid: 8855518
references.citation: Brain Res. 1980 Jul 7;193(1):153-63
references.pmid: 7378814
references.citation: Neurobiol Learn Mem. 2007 Jul;88(1):75-81
references.pmid: 17467309
references.citation: Neuropsychopharmacology. 2005 Nov;30(11):2026-34
references.pmid: 15900317
references.citation: J Neurosci. 2000 Jun 1;20(11):3993-4001
references.pmid: 10818134
references.citation: Synapse. 2003 Aug;49(2):89-96
references.pmid: 12740864
references.citation: Eur J Neurosci. 2007 Jul;26(1):228-41
references.pmid: 17614950
references.citation: Neuroscience. 2001;103(2):405-12
references.pmid: 11246155
references.citation: J Neurosci. 1999 Jun 1;19(11):4585-94
references.pmid: 10341256