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Adaptive fitness; early life adversity improves adult stress coping in heterozygous serotonin transporter knockout rats

Molecular Psychiatry volume 18, pages 1244–1245 (2013)Cite this article

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Early life adversity in the form of childhood abuse has been associated with increased risk for the development of psychiatric disorders such as major depression.1, 2 Recent reviews, however, have postulated the match/mismatch hypothesis of disease, which states that early life stress (ELS) is not necessarily pathological but can be of adaptive value.3, 4 Central to this hypothesis is the concept of the predictive adaptive response (PAR),5 which entails that an individual uses the experience of past stressors to adaptively respond to future stressors. PAR is expected to be most pronounced in stress-sensitive individuals, similar to humans carrying the low activity short (s) allelic variant of the serotonin transporter (5-HTT) promoter polymorphism (5-HTTLPR) and 5-HTT knockout rodents modeling this polymorphism.6 In this study, we used the maternal separation paradigm to test the hypothesis that ELS can improve adult stress coping behavior as a function of serotonin transporter gene variation.

The methods are fully available in the Supplementary Materials. Briefly, from postnatal day 2 to 14 litters were either exposed to a daily 180 min maternal separation (MS180) or a control treatment, which involved the exact same handling, but immediate reunion of dam and pups (MS0). Adult male offspring was subjected to inescapable (IS) shock stress in a shuttle-box (model ENV-010MD, Med Associates, St Albans, VT, USA). For 2 consecutive days, rats received 50 IS, unpredictable 0.6 mA foot shocks. Exactly 24 h after the start of the second exposure to IS, the rats were tested for 30 consecutive trials in which they could escape shocks by moving to the opposite end of the shuttle-box. The latency to escape the shocks was automatically recorded and the maximum of 15 s was registered in case of escape failure.

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Author notes

  1. T Kozicz and J R Homberg: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cellular Animal Physiology, Radboud University Nijmegen, Nijmegen, The Netherlands

    R H A van der Doelen & T Kozicz

  2. Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands

    R H A van der Doelen & J R Homberg

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  1. R H A van der Doelen
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  2. T Kozicz
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  3. J R Homberg
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Correspondence to J R Homberg.

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van der Doelen, R., Kozicz, T. & Homberg, J. Adaptive fitness; early life adversity improves adult stress coping in heterozygous serotonin transporter knockout rats. Mol Psychiatry 18, 1244–1245 (2013). https://doi.org/10.1038/mp.2012.186

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