Adult life behavioral consequences of early maternal separation are alleviated by escitalopram treatment in a rat model of depression

被引:108
作者
El Khoury, A
Gruber, SHM
Mork, A
Mathé, AA
机构
[1] Karolinska Univ Hosp Huddinge, Inst Clin Neurosci, Karolinska Inst, S-14186 Huddinge, Sweden
[2] H Lundbeck & Co AS, Dept Neurochem, DK-2500 Copenhagen, Denmark
关键词
depression; early maternal separation; escitalopram; flinders resistant line rat; flinders sensitive line rat; porsolt swim test;
D O I
10.1016/j.pnpbp.2005.11.011
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
In order to study the gene-environment interaction as well as investigate prophylactic/ameliorative effects of early intervention on development of adult life psychopathology, we superimposed maternal separation on an animal model of depression the Flinders Sensitive Line (FSL) rats and their controls the Flinders Resistant Line (FRL) rats and studied behavior following treatment with escitalopram. Animals were maternally separated for 180 min/day from postnatal day 2 (PND 2) to 14. The control groups were left undisturbed. Treatment with escitalopram or vehicle admixed to food pellets was commenced on PND 43 and continued until PND 73. The Porsolt swim test was carried out on PND 65. Baseline FRL/ FSL differences in body weight and swim duration, considered to be an inverse index of depression, were found (p's < 0.001). In the FSL, maternal separation further decreased swim duration (p < 0.001) while the FRL strain was unaffected. Escitalopram had no effect in FRL, but increased swim duration in both maternally non-separated and separated FSL (p < 0.05 and p=0.001; respectively). These results confirm the strain differences between the FSL and FRL and demonstrate that the long-term effects of early life adverse experience will to a significant degree depend on the genetic make-up of an individual. Finally, antidepressant treatment reversed behavioral abnormalities caused by genetic and environmental factors. This study highlights the importance of genetic factors in susceptibility to early life adverse events, and demonstrates the efficiency of early antidepressant treatment in reversing behavioral abnormalities, both those caused by genetic factors and by environmental factors. (c) 2005 Elsevier Inc. All rights reserved.
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收藏
页码:535 / 540
页数:6
相关论文
共 41 条
[1]   Environment and vulnerability to major psychiatric illness: a case control study of early parental loss in major depression, bipolar disorder and schizophrenia [J].
Agid, O ;
Shapira, B ;
Zislin, J ;
Ritsner, M ;
Ritsner, M ;
Hanin, B ;
Murad, H ;
Troudart, T ;
Bloch, M ;
Heresco-Levy, U ;
Lerer, B .
MOLECULAR PSYCHIATRY, 1999, 4 (02) :163-172
[2]  
[Anonymous], 2001, HDB PHYSL ENDOCR S23
[3]   Escitalopram [J].
Aronson, S ;
Delgado, P .
DRUGS OF TODAY, 2004, 40 (02) :121-131
[4]  
BOWLBY J, 1951, Bull World Health Organ, V3, P355
[5]  
Culpepper Larry, 2002, Prim Care Companion J Clin Psychiatry, V4, P209
[6]   ACTIVE BEHAVIORS IN THE RAT FORCED SWIMMING TEST DIFFERENTIALLY PRODUCED BY SEROTONERGIC AND NORADRENERGIC ANTIDEPRESSANTS [J].
DETKE, MJ ;
RICKELS, M ;
LUCKI, I .
PSYCHOPHARMACOLOGY, 1995, 121 (01) :66-72
[7]   The long-term effects of maternal deprivation depend on the genetic background [J].
Ellenbroek, BA ;
Cools, AR .
NEUROPSYCHOPHARMACOLOGY, 2000, 23 (01) :99-106
[8]   Anxiolytic-like effects of escitalopram, citalopram, and R-citalopram in maternally separated mouse pups [J].
Fish, EW ;
Faccidomo, S ;
Gupta, S ;
Miczek, KA .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2004, 308 (02) :474-480
[9]  
Francis DD, 2002, J NEUROSCI, V22, P7840
[10]   Social deprivation of neonatal, adolescent, and adult rats has distinct neurochemical and behavioral consequences [J].
Hall, FS .
CRITICAL REVIEWS IN NEUROBIOLOGY, 1998, 12 (1-2) :129-162