Effects of mild early life stress on abnormal emotion-related behaviors in 5-HTT knockout mice

被引:72
作者
Carroll, Jenna C.
Boyce-Rustay, Janel M.
Millstein, Rachel
Yang, Rebecca
Wiedholz, Lisa M.
Murphy, Dennis L.
Holmes, Andrew [1 ]
机构
[1] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA
[2] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA
关键词
5-HT; serotonin transporter; anxiety; depression; gene; mouse;
D O I
10.1007/s10519-006-9129-9
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
A low-expressing polymorphic variant of the serotonin transporter (5-HTT) gene has been associated with emotional disorders in humans and non-human primates following exposure to early life trauma. 5-HTT gene knockout (KO) mice exhibit increased anxiety- and depression-related behaviors, and provide a model to study interactions between 5-HTT gene variation and early life stress. The present study assessed the effects of postnatal footshock stress on the development of emotion-related behaviors in 5-HTT KO mice. Results showed that 5-HTT KO mice displayed a profile of suppressed exploratory behavior and increased anxiety-like behavior in the light/dark, elevated plus-maze and open field tests, as well as increased depression-related behavior in the forced swim test following repeated exposure to the test. Postnatal exposure to footshock stress did not affect emotion-related behaviors in non-mutant C57BL/6J mice or modify phenotypic abnormalities in 5-HTT KO. Data provide further evidence of emotional abnormalities following genetic disruption of the 5-HTT.
引用
收藏
页码:214 / 222
页数:9
相关论文
共 44 条
[1]   Vulnerability to mild predator stress in serotonin transporter knockout mice [J].
Adamec, Robert ;
Burton, Paul ;
Blundell, Jacqueline ;
Murphy, Dennis L. ;
Holmes, Andrew .
BEHAVIOURAL BRAIN RESEARCH, 2006, 170 (01) :126-140
[2]   Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus [J].
Amat, J ;
Baratta, MV ;
Paul, E ;
Bland, ST ;
Watkins, LR ;
Maier, SF .
NATURE NEUROSCIENCE, 2005, 8 (03) :365-371
[3]   Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice [J].
Ansorge, MS ;
Zhou, MM ;
Lira, A ;
Hen, R ;
Gingrich, JA .
SCIENCE, 2004, 306 (5697) :879-881
[4]   Sexual dichotomy of an interaction between early adversity and the serotonin transporter gene promoter variant in rhesus macaques [J].
Barr, CS ;
Newman, TK ;
Schwandt, M ;
Shannon, C ;
Dvoskin, RL ;
Lindell, SG ;
Taubman, J ;
Thompson, B ;
Champoux, M ;
Lesch, KP ;
Goldman, D ;
Suomi, SJ ;
Higley, JD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (33) :12358-12363
[5]   Altered brain serotonin homeostasis and locomotor insensitivity to 3,4-methylenedioxymethamphetamine ("ecstasy") in serotonin transporter-deficient mice [J].
Bengel, D ;
Murphy, DL ;
Andrews, AM ;
Wichems, CH ;
Feltner, D ;
Heils, A ;
Mössner, R ;
Westphal, H ;
Lesch, KP .
MOLECULAR PHARMACOLOGY, 1998, 53 (04) :649-655
[6]   CLONING AND EXPRESSION OF A FUNCTIONAL SEROTONIN TRANSPORTER FROM RAT-BRAIN [J].
BLAKELY, RD ;
BERSON, HE ;
FREMEAU, RT ;
CARON, MG ;
PEEK, MM ;
PRINCE, HK ;
BRADLEY, CC .
NATURE, 1991, 354 (6348) :66-70
[7]  
BOYCE WT, 1990, J DEV BEHAV PEDIATR, V11, P105
[8]   Genetic inactivation of the NMDA receptor NR2A subunit has anxiolytic- and antidepressant-like effects in mice [J].
Boyce-Rustay, Janel M. ;
Holmes, Andrew .
NEUROPSYCHOPHARMACOLOGY, 2006, 31 (11) :2405-2414
[9]   Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene [J].
Caspi, A ;
Sugden, K ;
Moffitt, TE ;
Taylor, A ;
Craig, IW ;
Harrington, H ;
McClay, J ;
Mill, J ;
Martin, J ;
Braithwaite, A ;
Poulton, R .
SCIENCE, 2003, 301 (5631) :386-389
[10]   Role of genotype in the cycle of violence in maltreated children [J].
Caspi, A ;
McClay, J ;
Moffitt, TE ;
Mill, J ;
Martin, J ;
Craig, IW ;
Taylor, A ;
Poulton, R .
SCIENCE, 2002, 297 (5582) :851-854