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Chronic stress selectively reduces hippocampal volume in rats: a longitudinal magnetic resonance imaging study

Lee, Taekwana; Jarome, Tima; Li, Shi-Jiangb; Kim, Jeansok J.c; Helmstetter, Fred J.a

doi: 10.1097/WNR.0b013e328332bb09

The notion of uncontrollable stress causing reduced hippocampal size remains controversial in the posttraumatic stress disorder literature, because human studies cannot discern the causality of effect. Here, we addressed this issue by using structural magnetic resonance imaging in rats to measure the hippocampus and other brain regions before and after stress. Chronic restraint stress produced approximately 3% reduction in hippocampal volume, which was not observed in control rats. This decrease was not signficantly correlated with baseline hippocampal volume or body weight. Total forebrain volume and the sizes of the other brain regions and adrenal glands were all unaffected by stress. This longitudinal, within-subjects design study provides direct evidence that the hippocampus is differentially vulnerable and sensitive to chronic stress.

aDepartment of Psychology, Garland Hall, University of Wisconsin

bDepartment of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin

cDepartment of Psychology and Program in Neurobiology and Behavior, Guthrie Hall, University of Washington, Seattle, Washington, USA

Correspondence to Dr Fred J. Helmstetter, Department of Psychology, Garland Hall, University of Wisconsin, Milwaukee, Wisconsin 53201, USA

Tel: +1 414 229 4979; fax: +1 414 229 2912; e-mail:

Received 4 June 2009 accepted 4 September 2009

© 2009 Lippincott Williams & Wilkins, Inc.