title: Exploratory, anxiety and spatial memory impairments are dissociated in mice lacking the LPA1 receptor.
abstract: Lysophosphatidic acid (LPA) is a new, intercellular signalling molecule in the brain that has an important role in adult hippocampal plasticity. Mice lacking the LPA(1) receptor exhibit motor, emotional and cognitive alterations. However, the potential relationship among these concomitant impairments was unclear. Wild-type and maLPA(1)-null mice were tested on the hole-board for habituation and spatial learning. MaLPA(1)-null mice exhibited reduced exploration in a novel context and a defective intersession habituation that also revealed increased anxiety-like behaviour throughout the hole-board testing. In regard to spatial memory, maLPA(1) nulls failed to reach the controls' performance at the end of the reference memory task. Moreover, their defective working memory on the first training day suggested a delayed acquisition of the task's working memory rule, which is also a long term memory component. The temporal interval between trials and the task's difficulty may explain some of the deficits found in these mice. Principal components analysis revealed that alterations found in each behavioural dimension were independent. Therefore, exploratory and emotional impairments did not account for the cognitive deficits that may be attributed to maLPA(1) nulls' hippocampal malfunction.
authors.affiliation: Departamento de Psicobiología y Metodología de las CC, Universidad de Málaga, Campus de Teatinos, 29071 Málaga, Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Castilla-Ortega
authors.forename: Jorge
authors.initials: J
authors.lastname: Sánchez-López
authors.forename: Carolina
authors.initials: C
authors.lastname: Hoyo-Becerra
authors.forename: Elisa
authors.initials: E
authors.lastname: Matas-Rico
authors.forename: Emma
authors.initials: E
authors.lastname: Zambrana-Infantes
authors.forename: Jerold
authors.initials: J
authors.lastname: Chun
authors.forename: Fernando Rodríguez
authors.initials: FR
authors.lastname: De Fonseca
authors.forename: Carmen
authors.initials: C
authors.lastname: Pedraza
authors.forename: Guillermo
authors.initials: G
authors.lastname: Estivill-Torrús
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Santin
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology*; D006185:Habituation, Psychophysiologic / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism*; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009483:Neuropsychological Tests; D025341:Principal Component Analysis; D049368:Receptors, Lysophosphatidic Acid / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013028:Space Perception / Q000502:physiology; D013997:Time Factors
chemical_list: D049368:Receptors, Lysophosphatidic Acid
references.citation: Behav Brain Res. 1994 Mar 31;61(1):59-64
references.pmid: 7913324
references.citation: Psychopharmacology (Berl). 2007 May;192(1):39-48
references.pmid: 17242924
references.citation: Nat Neurosci. 2003 Dec;6(12):1292-9
references.pmid: 14625558
references.citation: Brain Res Cogn Brain Res. 1996 Jun;3(3-4):167-81
references.pmid: 8806020
references.citation: Bioessays. 2004 Aug;26(8):870-81
references.pmid: 15273989
references.citation: Genes Brain Behav. 2007 Jun;6(4):389-400
references.pmid: 16939636
references.citation: Hippocampus. 2006;16(3):216-24
references.pmid: 16421862
references.citation: Exp Neurol. 2006 Feb;197(2):330-40
references.pmid: 16309676
references.citation: Prostaglandins Other Lipid Mediat. 2005 Sep;77(1-4):46-51
references.pmid: 16099390
references.citation: Pharmacol Biochem Behav. 1998 Jun;60(2):473-88
references.pmid: 9632231
references.citation: Cereb Cortex. 2008 Apr;18(4):938-50
references.pmid: 17656621
references.citation: Biol Psychiatry. 2000 Dec 15;48(12):1157-63
references.pmid: 11137057
references.citation: Brain Res Bull. 1981 Aug;7(2):221-6
references.pmid: 7272800
references.citation: Behav Neurosci. 2002 Jun;116(3):464-71
references.pmid: 12049327
references.citation: Neuropsychologia. 1979;17(6):669-82
references.pmid: 522981
references.citation: Genes Brain Behav. 2004 Jun;3(3):149-57
references.pmid: 15140010
references.citation: Behav Neurosci. 2003 Oct;117(5):1044-53
references.pmid: 14570553
references.citation: Learn Mem. 2008 Feb 19;15(3):97-105
references.pmid: 18285468
references.citation: Rev Physiol Biochem Pharmacol. 2008;160:25-46
references.pmid: 18481029
references.citation: Neurosci Biobehav Rev. 1998;22(1):33-57
references.pmid: 9491939
references.citation: Neurobiol Learn Mem. 2006 Sep;86(2):150-9
references.pmid: 16580234
references.citation: Curr Drug Targets. 2007 Jan;8(1):155-67
references.pmid: 17266539
references.citation: Nature. 1982 Jun 24;297(5868):681-3
references.pmid: 7088155
references.citation: Cell Mol Life Sci. 2006 Dec;63(23):2695-701
references.pmid: 16988788
references.citation: J Biol Chem. 2004 May 14;279(20):20555-8
references.pmid: 15023998
references.citation: Annu Rev Biochem. 2004;73:321-54
references.pmid: 15189145
references.citation: Genes Brain Behav. 2009 Nov;8(8):772-84
references.pmid: 19689455
references.citation: Eur J Neurosci. 1998 Mar;10(3):1045-53
references.pmid: 9753172
references.citation: Brain Res. 1997 Aug 8;765(1):37-50
references.pmid: 9310392
references.citation: Behav Brain Res. 2002 Aug 21;134(1-2):49-57
references.pmid: 12191791
references.citation: Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13384-9
references.pmid: 11087877
references.citation: Psychoneuroendocrinology. 1998 Jan;23(1):33-44
references.pmid: 9618750
references.citation: Mol Cell Neurosci. 2003 Dec;24(4):1170-9
references.pmid: 14697676
references.citation: J Neurosci. 2001 Nov 15;21(22):9077-81
references.pmid: 11698618
references.citation: Brain Res. 1971 Nov;34(1):171-5
references.pmid: 5124915
references.citation: J Neurochem. 2006 Jun;97(5):1379-92
references.pmid: 16638019
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4642-6
references.pmid: 17360577
references.citation: Neurosci Biobehav Rev. 2006;30(7):1045-64
references.pmid: 16774787
references.citation: Curr Opin Pharmacol. 2009 Feb;9(1):15-23
references.pmid: 19119080
references.citation: Neuroreport. 2006 Apr 3;17(5):523-6
references.pmid: 16543818
references.citation: Mol Cell Neurosci. 2008 Nov;39(3):342-55
references.pmid: 18708146
references.citation: Eur J Pharmacol. 1998 May 29;350(1):21-9
references.pmid: 9683010
references.citation: Eur J Neurosci. 2004 Jun;19(12):3151-64
references.pmid: 15217371
references.citation: Eur J Neurosci. 2003 Jan;17(1):128-36
references.pmid: 12534976
references.citation: Biochim Biophys Acta. 2008 Sep;1781(9):531-9
references.pmid: 18407842
references.citation: Neuroscience. 1999;93(1):243-51
references.pmid: 10430488
references.citation: Behav Brain Res. 2006 Mar 15;168(1):92-9
references.pmid: 16310870
references.citation: Learn Mem. 2002 Sep-Oct;9(5):224-37
references.pmid: 12359832
references.citation: J Neurosci. 2006 Mar 8;26(10):2767-76
references.pmid: 16525056
references.citation: Learn Mem. 2003 Mar-Apr;10(2):108-15
references.pmid: 12663749
references.citation: Behav Brain Res. 1998 Mar;91(1-2):73-81
references.pmid: 9578441
references.citation: Neurochem Res. 2005 Mar;30(3):371-7
references.pmid: 16018581
references.citation: Annu Rev Pharmacol Toxicol. 2001;41:507-34
references.pmid: 11264467
references.citation: Neurobiol Learn Mem. 1999 Sep;72(2):78-94
references.pmid: 10438649
references.citation: Eur J Neurosci. 2006 Jul;24(2):595-605
references.pmid: 16903861
references.citation: Pharmacol Biochem Behav. 1999 Dec;64(4):731-8
references.pmid: 10593196
references.citation: Mol Cell Neurosci. 2002 Jun;20(2):271-82
references.pmid: 12093159
references.citation: Learn Mem. 2008 Oct 02;15(10):733-46
references.pmid: 18832560
references.citation: Hippocampus. 1998;8(2):138-46
references.pmid: 9572720
references.citation: Annu Rev Pharmacol Toxicol. 2010;50:157-86
references.pmid: 20055701
references.citation: Behav Pharmacol. 2005 May;16(3):171-80
references.pmid: 15864072
references.citation: Schizophr Res. 2006 Feb 28;82(2-3):175-83
references.pmid: 16414245