Adverse early life experience and social stress during adulthood interact to increase serotonin transporter mRNA expression

被引:62
作者
Gardner, Katherine L. [2 ]
Hale, Matthew W. [1 ]
Lightman, Stafford L. [2 ]
Plotsky, Paul M. [3 ]
Lowry, Christopher A. [1 ,2 ]
机构
[1] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA
[2] Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Bristol, Avon, England
[3] Emory Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
Anxiety; Depression; Maternal separation; Raphe; Serotonin; Stress; DORSAL RAPHE NUCLEUS; NEONATAL MATERNAL SEPARATION; C-FOS EXPRESSION; LONG-LASTING CHANGES; MAJOR DEPRESSION; RAT-BRAIN; GLUCOCORTICOID-RECEPTOR; AFFERENT-PROJECTIONS; PERIAQUEDUCTAL GRAY; EMOTIONAL BEHAVIOR;
D O I
10.1016/j.brainres.2009.09.065
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Anxiety disorders, depression and animal models of vulnerability to a depression-like syndrome have been associated with dysregulation of serotonergic systems in the brain. To evaluate the effects of early life experience, adverse experiences during adulthood, and potential interactions between these factors on serotonin transporter (slc6a4) mRNA expression, we investigated in rats the effects of maternal separation (180 min/day from days 2 to 14 of life; MS180), neonatal handing (15 min/day from days 2 to 14 of life; MS15), or normal animal facility rearing (AFR) control conditions with or without subsequent exposure to adult social defeat on slc6a4 mRNA expression in the dorsal raphe nucleus (DR) and caudal linear nucleus. At the level of specific subdivisions of the DR, there were no differences in slc6a4 mRNA expression between MS15 and AFR rats. Among rats exposed to a novel cage control condition, increased slc6a4 mRNA expression was observed in the dorsal part of the DR in MS180 rats, relative to AFR control rats. In contrast, MS180 rats exposed to social defeat as adults had increased slc6a4 mRNA expression throughout the DR compared to both MS15 and AFR controls. Social defeat increased slc6a4 mRNA expression, but only in MS180 rats and only in the "lateral wings" of the DR. Overall these data demonstrate that early life experience and stressful experience during adulthood interact to determine slc6a4 mRNA expression. These data support the hypothesis that early life experience and major stressful life events contribute to dysregulation of serotonergic systems in stress-related neuropsychiatric disorders. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:47 / 63
页数:17
相关论文
共 109 条
[1]   Anatomic and functional topography of the dorsal raphe nucleus [J].
Abrams, JK ;
Johnson, PL ;
Hollis, JH ;
Lowry, CA .
STRESS: CURRENT NEUROENDOCRINE AND GENETIC APPROACHES, 2004, 1018 :46-57
[2]   Serotonergic systems associated with arousal and vigilance behaviors following administration of anxiogenic drugs [J].
Abrams, JK ;
Johnson, PL ;
Hay-Schmidt, A ;
Mikkelsen, JD ;
Shekhar, A ;
Lowry, CA .
NEUROSCIENCE, 2005, 133 (04) :983-997
[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]   Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims [J].
Arango, V ;
Underwood, MD ;
Boldrini, M ;
Tamir, H ;
Kassir, SA ;
Hsiung, SC ;
Chen, JJX ;
Mann, JJ .
NEUROPSYCHOPHARMACOLOGY, 2001, 25 (06) :892-903
[5]   Increased responsiveness of presumed 5-HT cells to citalopram in adult rats subjected to prolonged maternal separation relative to brief separation [J].
Arborelius, L ;
Hawks, BW ;
Owens, MJ ;
Plotsky, PM ;
Nemeroff, CB .
PSYCHOPHARMACOLOGY, 2004, 176 (3-4) :248-U5
[6]   Elevated expression of tryptophan hydroxylase-2 mRNA at the neuronal level in the dorsal and median raphe nuclei of depressed suicides [J].
Bach-Mizrachi, H. ;
DUnderwood, M. ;
Tin, A. ;
PEllis, S. ;
Mann, J. J. ;
Arango, V. .
MOLECULAR PSYCHIATRY, 2008, 13 (05) :507-513
[7]   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
[8]   Brief vs. long maternal separations in infancy: contrasting relationships with adult maternal behavior and lactation levels of aggression and anxiety [J].
Boccia, ML ;
Pedersen, CA .
PSYCHONEUROENDOCRINOLOGY, 2001, 26 (07) :657-672
[9]   Inputs to Serotonergic Neurons Revealed by Conditional Viral Transneuronal Tracing [J].
Braz, Joao M. ;
Enquist, Lynn W. ;
Basbaum, Allan I. .
JOURNAL OF COMPARATIVE NEUROLOGY, 2009, 514 (02) :145-160
[10]   THE EFFECT OF CHRONIC IMIPRAMINE ADMINISTRATION ON THE DENSITIES OF 5-HT1A AND 5-HT2 RECEPTORS AND THE ABUNDANCIES OF 5-HT RECEPTOR AND TRANSPORTER MESSENGER-RNA IN THE CORTEX, HIPPOCAMPUS AND DORSAL RAPHE OF 3 STRAINS OF RAT [J].
BURNET, PWJ ;
MICHELSON, D ;
SMITH, MA ;
GOLD, PW ;
STERNBERG, EM .
BRAIN RESEARCH, 1994, 638 (1-2) :311-324