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PNAS 106 (22): 9069-9074

Copyright © 2009 by the National Academy of Sciences.


Peripheral tumors induce depressive-like behaviors and cytokine production and alter hypothalamic-pituitary-adrenal axis regulation

Leah M. Pyter1, Vanessa Pineros, Jerome A. Galang, Martha K. McClintock, and Brian J. Prendergast

Department of Psychology, Institute for Mind and Biology, University of Chicago, 940 East 57th Street, Chicago, IL 60637

Edited by Bruce S. McEwen, The Rockefeller University, New York, NY, and approved April 15, 2009

Received for publication November 24, 2008.

Abstract: A strong and positive correlation exists between chronic disease and affective disorders, but the biological mechanisms underlying this relationship are not known. Here we show that rats with mammary cancer exhibit depression- and anxiety-like behaviors in the absence of overt sickness behaviors. The production of proinflammatory cytokines, known to induce depressive-like behaviors, was elevated in the periphery and in the hippocampus of rats with tumors compared with controls. In tumor-bearing rats, circulating corticosterone, which inhibits cytokine signaling, was suppressed following a stressor, and gene expression of hippocampal glucocorticoid receptors was elevated. The results establish that tumors alone are sufficient to trigger changes in emotional behaviors. Dampened glucocorticoid responses to stressors may exacerbate the deleterious effects of tumor-induced cytokines on affective states.

Key Words: cancer • depression • HPA • hippocampus

Author contributions: L.M.P. and B.J.P. designed research; L.M.P., V.P., J.A.G., and B.J.P. performed research; M.K.M. contributed new reagents/analytic tools; L.M.P. and B.J.P. analyzed data; and L.M.P. and B.J.P. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

1To whom correspondence should be addressed. E-mail: pyter{at}

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