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Prenatal stress produces sex-specific changes in depression-like behavior in rats: implications for increased vulnerability in females

Published online by Cambridge University Press:  08 July 2015

H. M. Sickmann ,
T. S. Arentzen ,
T. B. Dyrby ,
N. Plath  and
M. P. Kristensen
H. M. Sickmann*
Affiliation:
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark H. Lundbeck, Synaptic Transmission, Valby, Denmark Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
T. S. Arentzen
Affiliation:
H. Lundbeck, Synaptic Transmission, Valby, Denmark
T. B. Dyrby
Affiliation:
Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
N. Plath
Affiliation:
H. Lundbeck, Synaptic Transmission, Valby, Denmark
M. P. Kristensen
Affiliation:
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
*
*Address for correspondence: H. M. Sickmann, Department of Drug Design and Pharmacology, Jagtvej 160, DK-2100 Copenhagen Ø, Denmark. (Email hellesickmann@hotmail.com)
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Abstract

Stress during rat gestation can elicit depression-like physiological and behavioral responses in the offspring. However, human clinical depression is more prevalent among females than males. Accordingly, we examined how repeated variable prenatal stress (PS) alters rat anxiety- and depression-like behavior as well as circadian patterning of motor activity in both male and female offspring. For this purpose, we exposed pregnant Sprague–Dawley rats to multiple stressors during gestational days 13–21. Subsequently, we monitored locomotor and rearing/climbing activities in home-like cages for 24 h and measured anxiety- (elevated plus maze, EPM) and depression-like (forced swim test, FST) behaviors in the offspring at a young adult age. As a stressful event later in life (in addition to PS) may be needed to actually trigger an episode of clinical depression, half of the animals were exposed to an acute stressor (elevated platform) before EPM testing. Dams exposed to the stressor battery had increased plasma corticosterone levels compared with controls. Male PS offspring displayed changes in locomotor and rearing/climbing activity relative to controls. Additionally, anxiety measures in the EPM were affected in control animals after acute stressor exposure, however, this response was blunted in PS offspring. Moreover, FST immobility, as an indicator of depressive-like behavior, was increased in female but not male PS rats. Altogether, our results identify both sex- and circadian phase-specific effects of PS. These findings indicate that the PS rat model reflects multiple clinical depression characteristics, including elevated female vulnerability.

Keywords

elevated plus mazeforced swim testHPA axislocomotor and rearing/climbing activitysex differences
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 6 , Issue 5: Themed Issue: David Barker commemorative meeting, September 2014; Prenatal Exposures and Health Outcomes , October 2015 , pp. 462 - 474
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2015 

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