General and social anxiety in the BTBR T+ tf/J mouse strain.
BTBR T+ tf/J (BTBR) is an inbred mouse strain that shows behavioral traits with analogies to the three diagnostic symptoms of autism spectrum disorder (ASD); deficits in social interaction, impaired communication, and repetitive behaviors with restricted interests. Previous findings reveal that when compared to C57BL/6J (B6) and other inbred strains, BTBR exhibit normal to low anxiety-like traits in paradigms designed to assess anxiety-related behaviors. The current study assessed the generality of these anxiety findings. In experiment 1, B6 and BTBR mice were tested in the elevated plus maze (EPM), mouse defense test battery (MDTB) and elevated zero-maze. BTBR mice exhibited an anxiogenic profile in the EPM, with a reduction in open arm time and an increase in risk assessment behaviors, as compared to B6. In the MDTB, BTBR showed enhanced vocalization to the predator, and significantly less locomotor activity than B6 in the pre-threat situation, but significantly more locomotion than B6 following exposure to a predator threat, suggesting enhanced defensiveness to the predator. In the zero-maze, BTBR mice showed a significantly higher number of entries and time spent in the open segments of the apparatus, when compared to B6. In experiment 2, a three-chambered social preference test was used to evaluate effects of the systemic administration of an anxiolytic compound, diazepam, on B6 and BTBR social approach. Diazepam consistently increased time in the compartment containing the social stimulus, for both B6 and BTBR mice. However, in the vehicle treated groups, B6 mice spent significantly more time while BTBR mice spent significantly less time in the social stimulus compartment; after diazepam administration both B6 and BTBR strains significantly preferred the social stimulus chamber. These results suggest that while the anxiety responses of BTBR mice to novel situations (EPM and zero-maze) are inconsistent, BTBR mice appear to be more defensive to animate threat stimuli (predator or another mouse). Reduction of anxiety by diazepam normalized the social preference of BTBR for a mouse stimulus in the three-chambered test.
Pobbe
Roger L H
RL
Pacific Biosciences Research Center, University of Hawaii,1993 East-West Road, Honolulu, HI 96822, USA. rogerlh@hawaii.edu
Defensor
Erwin B
EB
Pearson
Brandon L
BL
Bolivar
Valerie J
VJ
Blanchard
D Caroline
DC
Blanchard
Robert J
RJ
D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology*; D005106:Exploratory Behavior / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000502:physiology*; D010641:Phenotype; D012919:Social Behavior; D013045:Species Specificity
Psychopharmacology (Berl). 1998 Jul;138(1):55-66
9694527
Trends Genet. 2002 Dec;18(12):643-50
12446150
Br Med J. 1975 Apr 5;2(5961):36-7
1137783
J Neurosci. 2006 Jun 28;26(26):6897-906
16807320
Am J Hum Genet. 2005 Jan;76(1):68-81
15547804
Funct Neurol. 1987 Jul-Sep;2(3):355-61
2826308
Brain Res. 2001 Jan 12;888(2):311-313
11150490
Psychopharmacology (Berl). 1987;92(2):180-5
3110839
Drug Metabol Drug Interact. 1990;8(1-2):31-83
2091890
Nature. 2009 May 28;459(7246):569-73
19404257
Mamm Genome. 2001 Oct;12(10):755-7
11678137
Eur J Neurosci. 2009 Apr;29(8):1663-77
19419429
Behav Brain Res. 2011 Jan 1;216(1):19-28
20540967
Nat Rev Neurosci. 2010 Jul;11(7):490-502
20559336
Genes Brain Behav. 2009 Mar;8(2):129-42
19016890
Arch Pediatr Adolesc Med. 2007 Apr;161(4):372-7
17404134
Genes Brain Behav. 2011 Feb;10(1):35-43
20345893
Int J Dev Neurosci. 2007 Dec;25(8):515-21
17980995
J Child Psychol Psychiatry. 2004 Jan;45(1):135-70
14959806
Indian J Exp Biol. 2000 Apr;38(4):343-6
11218810
Neuropeptides. 2002 Apr-Jun;36(2-3):221-9
12359512
Pharmacol Biochem Behav. 2000 Dec;67(4):739-48
11166064
Mol Psychiatry. 2007 Jan;12(1):2-22
17033636
Behav Brain Res. 2009 Feb 11;197(2):462-5
18977396
Ment Retard Dev Disabil Res Rev. 2002;8(3):151-61
12216059
Psychopharmacology (Berl). 2000 Feb;148(2):164-70
10663431
Brain Res. 2008 May 19;1210:179-88
18417102
Genes Brain Behav. 2008 Apr;7(3):344-54
17908176
J Pharmacol Exp Ther. 1992 Jul;262(1):90-8
1352556
Eur J Pharmacol. 2003 Feb 28;463(1-3):97-116
12600704
J Psychopharmacol. 2007 Sep;21(7):774-82
17881433
Indian J Exp Biol. 2000 Jan;38(1):36-41
11233082
Neurosci Biobehav Rev. 2001 May;25(3):205-18
11378177
Behav Brain Res. 2007 Jan 10;176(1):53-65
16890300
BMC Public Health. 2004 Mar 03;4:5
15113435
Nature. 2008 Dec 11;456(7223):724-7
19079048
Mol Psychiatry. 2008 Jan;13(1):4-26
17848915
Brain Pathol. 2007 Oct;17(4):448-59
17919130
Behav Brain Res. 2007 Jan 10;176(1):21-6
17097158
Behav Brain Res. 2009 Dec 1;204(1):217-25
19527754
Neurotoxicology. 2009 Sep;30(5):811-21
19596370
Neurosci Biobehav Rev. 1985 Spring;9(1):37-44
2858080
Behav Brain Res. 2007 Jan 10;176(1):4-20
16971002
Pharmacol Biochem Behav. 1980 Jul;13(1):27-30
7190708
Physiol Behav. 2010 Jun 1;100(3):264-7
20298706
Front Behav Neurosci. 2007 Nov 02;1:1
18958184
Pediatrics. 2004 May;113(5):e472-86
15121991
Physiol Behav. 2010 Jun 1;100(3):268-76
20093134
Psychopharmacology (Berl). 2009 Mar;202(4):711-8
18923820
Nat Neurosci. 2005 Apr;8(4):519-26
15750588
Nat Rev Genet. 2008 May;9(5):341-55
18414403
Behav Brain Res. 2008 Aug 5;191(1):118-29
18440079
Genes Brain Behav. 2004 Oct;3(5):287-302
15344922
Am J Med Genet B Neuropsychiatr Genet. 2007 Jul 5;144B(5):581-8
17219386
Braz J Med Biol Res. 1997 Mar;30(3):289-304
9246227
Trends Neurosci. 2006 Jul;29(7):349-358
16808981
PLoS One. 2008 Aug 27;3(8):e3067
18728777
Nat Rev Genet. 2001 Dec;2(12):943-55
11733747
Psychopharmacology (Berl). 1994 Sep;116(1):56-64
7862931
Nat Rev Genet. 2002 Feb;3(2):114-23
11836505
Genes Brain Behav. 2008 Mar;7(2):152-63
17559418
Psychol Med. 1995 Jan;25(1):63-77
7792363
Arch Gen Psychiatry. 2006 Jun;63(6):694-701
16754843
Clin Psychol Rev. 2009 Apr;29(3):216-29
19223098
Am J Med Genet. 2001 Jan 8;105(1):53-4
11424998