Adult life behavioral consequences of early maternal separation are alleviated by escitalopram treatment in a rat model of depression.
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.
El Khoury
Aram
A
Karolinska Institutet, Inst. of Clinical Neuroscience, Psychiatry M56, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden.
Gruber
Susanne H M
SH
Mørk
Arne
A
Mathé
Aleksander A
AA
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects*; D015283:Citalopram / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D008426:Maternal Deprivation; D011897:Random Allocation; D051381:Rats; D013550:Swimming
D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram