title: Differential regulation of locomotor activity to acute and chronic cocaine administration by acid-sensing ion channel 1a and 2 in adult mice.
abstract: Acid-sensing ion channels (ASICs) are densely expressed in the brain with ASIC1a and ASIC2 channels being the predominant subtypes. These channels are enriched at synaptic sites and are central for the regulation of normal synaptic transmission. Moreover, increasing evidence links ASICs to the pathogenesis of various neurological and neuropsychiatric disorders. In this study, we explore the putative role of ASIC1a and ASIC2 in the regulation of behavioral sensitivity to the psychostimulant cocaine by utilizing ASIC1a or ASIC2 knockout mice. Acute cocaine injection induced a typical dose-dependent increase in locomotor activities in wild-type (WT) mice. However, in ASIC1a and ASIC2 mutant mice, different motor responses to cocaine were observed. In ASIC1a(-/-) mice, cocaine induced a significantly less motor response at all doses (5, 10, 20, and 30 mg/kg), while in ASIC2(-/-) mice, cocaine (5-20 mg/kg) stimulated locomotor activity to an extent comparable to WT mice. Only at 30 mg/kg, the cocaine-stimulated motor activity was reduced in ASIC2(-/-) mice. In a chronic cocaine administration model (20mg/kg, once daily for 5 days), a challenge injection of cocaine (10mg/kg, after 2-week withdrawal) caused an evident behavioral sensitization in the cocaine-pretreated WT mice. This behavioral sensitization to challenge cocaine was also displayed in ASIC1a(-/-) and ASIC2(-/-) mice. However, ASIC2(-/-) mice showed less sensitization to challenge cocaine when compared to WT and ASIC1a(-/-) mice. Our results demonstrate the important role of ASIC1a and ASIC2 channels in the modulation of behavioral sensitivity to cocaine. The two synapse-enriched ASIC subtypes are believed to play distinguishable roles in the regulation of behavioral responses to acute and chronic cocaine administration.
authors: Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
authors: Q
authors: Q
authors: Jiang
authors: C M
authors: CM
authors: Wang
authors: E E
authors: EE
authors: Fibuch
authors: J Q
authors: JQ
authors: Wang
authors: X-P
authors: XP
authors: Chu
mesh_terms: D062565:Acid Sensing Ion Channels / Q000502:physiology*; D000367:Age Factors; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology*
chemical_list: C568267:ASIC1 protein, mouse; C568265:ASIC2 protein, mouse; D062565:Acid Sensing Ion Channels; D003042:Cocaine
references: Mol Psychiatry. 2011 Oct;16(10):974-86
references: 21519339
references: Nature. 2007 Sep 20;449(7160):316-23
references: 17882215
references: J Neurosci. 2004 Oct 6;24(40):8678-89
references: 15470133
references: Psychopharmacology (Berl). 2002 Aug;163(1):54-61
references: 12185400
references: Hum Mol Genet. 2008 Oct 15;17(20):3223-35
references: 18658163
references: Psychol Rev. 1987 Oct;94(4):469-92
references: 3317472
references: Neurosci Lett. 2009 Aug 14;459(3):119-22
references: 19427358
references: J Physiol. 2003 Jan 1;546(Pt 1):77-87
references: 12509480
references: Nat Neurosci. 2009 May;12(5):602-10
references: 19349975
references: Trends Neurosci. 2006 Nov;29(11):610-6
references: 16956674
references: Neuroscience. 2009 Aug 4;162(1):55-66
references: 19376200
references: Neurobiol Dis. 2001 Feb;8(1):45-58
references: 11162239
references: J Cereb Blood Flow Metab. 2001 Jun;21(6):734-40
references: 11488542
references: Nature. 1997 Mar 13;386(6621):173-7
references: 9062189
references: Biochim Biophys Acta. 2009 Nov;1787(11):1383-94
references: 19161976
references: Cell. 1997 Sep 19;90(6):991-1001
references: 9323127
references: Nature. 1998 Jul 9;394(6689):192-5
references: 9671304
references: Eur J Pharmacol. 2009 Oct 1;619(1-3):50-6
references: 19686726
references: Trends Neurosci. 2006 Oct;29(10):578-86
references: 16891000
references: Neurosci Res. 2010 Sep;68(1):1-8
references: 20566346
references: Curr Opin Pharmacol. 2008 Feb;8(1):25-32
references: 17945532
references: J Biol Chem. 2004 Apr 30;279(18):18296-305
references: 14960591
references: Proc Natl Acad Sci U S A. 1988 Jul;85(14):5274-8
references: 2899326
references: Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16556-61
references: 17060608
references: Science. 2005 Nov 25;310(5752):1340-3
references: 16311338
references: Nat Med. 2007 Dec;13(12):1483-9
references: 17994101
references: J Biol Chem. 2004 Mar 19;279(12):11006-15
references: 14701823
references: Cell. 2004 Sep 17;118(6):687-98
references: 15369669
references: Nature. 1995 Oct 5;377(6548):424-8
references: 7566118
references: Brain Res. 1981 Jun 9;214(1):150-4
references: 6263415
references: Int J Physiol Pathophysiol Pharmacol. 2010 Mar 18;2(2):73-94
references: 21383888
references: J Neurosci. 2003 Jul 2;23(13):5496-502
references: 12843249
references: Curr Opin Neurobiol. 2012 Jun;22(3):545-51
references: 22000687
references: Neuropsychopharmacology. 2010 Jan;35(1):27-47
references: 19675534
references: Nat Rev Neurosci. 2009 Aug;10(8):561-72
references: 19571793
references: Front Mol Neurosci. 2012 Jun 27;5:72
references: 22754497
references: Nat Neurosci. 2008 Jul;11(7):816-22
references: 18536711
references: Int J Physiol Pathophysiol Pharmacol. 2011;3(4):288-309
references: 22162785
references: J Neurosci. 1998 May 1;18(9):3470-9
references: 9547254
references: Curr Opin Neurobiol. 1998 Jun;8(3):418-24
references: 9687356
references: Trends Neurosci. 1991 Jul;14(7):299-302
references: 1719677
references: Curr Drug Targets. 2012 Feb;13(2):263-71
references: 22204324
references: J Neurosci. 2009 Jul 1;29(26):8438-46
references: 19571134
references: J Neurosci. 2012 Mar 21;32(12):4080-91
references: 22442073
references: Curr Opin Drug Discov Devel. 2009 Sep;12(5):693-704
references: 19736627
references: Neuron. 2002 Apr 25;34(3):463-77
references: 11988176
references: Neuropharmacology. 2004;47 Suppl 1:61-79
references: 15464126
references: Cell. 2009 Nov 25;139(5):1012-21
references: 19945383
references: Nat Rev Neurosci. 2007 Nov;8(11):844-58
references: 17948030
references: Neurobiol Dis. 2008 Sep;31(3):334-41
references: 18606547
references: Nat Neurosci. 2011 Jul 10;14(8):1033-8
references: 21743470
references: Neuron. 2005 Nov 23;48(4):635-46
references: 16301179
references: J Neurosci. 2011 Jun 29;31(26):9723-34
references: 21715637
references: J Neurosci. 2009 Apr 29;29(17):5381-8
references: 19403806
references: J Biol Chem. 1997 Nov 21;272(47):29778-83
references: 9368048