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Cerebral Cortex Advance Access published online on March 20, 2008

Cerebral Cortex, doi:10.1093/cercor/bhn035
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Effects of Long-Term Stress and Recovery on the Prefrontal Cortex and Dentate Gyrus in Male and Female Rats

Yanhua Lin1,2, Christel Westenbroek1, Petra Bakker1, Joan Termeer1, Aihua Liu2, Xuejun Li2 and Gert J. Ter Horst1

1 Department of Psychiatry, University Medical Center Groningen, University of Groningen, Graduate School of Behavioral and Cognitive Neurosciences, Hanzeplein 1, P.O. Box 30.001, 9700 RB Groningen, The Netherlands, 2 Department of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University, Beijing 100083, China

Address correspondence to Prof Gert J. Ter Horst, PhD, Department of Psychiatry, University Medical Center Groningen, University of Groningen, Graduate School of Behavioral and Cognitive Neurosciences, Hanzeplein 1, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. Email: g.j.ter.horst{at}med.umcg.nl.

Women show a higher prevalence for depression than men. However, the biological basis of gender differences in stress response and recovery still remain poorly understood. Therefore, the aim of the study was to assess the gender differences in response to acute stress, chronic stress and recovery in rats. Our results showed that stress decreased male body weight but had no effect on female rats. Open field test demonstrated behavioral changes in grooming and velocity after chronic stress and recovery. Increased activity of hypothalamic-pituitary-adrenocortical axis was reflected by adrenal hypertrophy and increase of plasma corticosterone levels except in the socially housed female rats after stress. Gender and brain region differences in response to stress and recovery were found in the expression of cAMP response element–binding protein (CREB) and phosphorylated CREB (pCREB). On the whole, expression of CREB and pCREB in male dentate gyrus (DG) and prefrontal cortex (PFC) was sensitive but in female DG and PFC it was resistant to acute and chronic stress. Interestingly, recovery restored the measured parameters to the normal level in male rats but not in female rats. In conclusion, these results suggest that male and female rats responded to stress and recovery in a different way.

Key Words: gender differences • neuroplasticity • recovery • social housing • stress response


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Y. Lin, G. J. Ter Horst, R. Wichmann, P. Bakker, A. Liu, X. Li, and C. Westenbroek
Sex Differences in the Effects of Acute and Chronic Stress and Recovery after Long-Term Stress on Stress-Related Brain Regions of Rats
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