Defeat, Distress, and Glucocorticoids

Science Signaling  22 Jan 2013:
Vol. 6, Issue 259, pp. ec23
DOI: 10.1126/scisignal.2003979

Understanding how individuals control emotions and cope with stressful events is a major clinical concern and of importance for the treatment of psychiatric illnesses (see the Perspective by McEwen). Barik et al. discovered that aggressive defeat stress in mice caused glucocortioid release and increased activity in the dopamine system. Deleting the glucocorticoid receptors in dopaminoceptive neurons completely prevented the social avoidance that usually follows aggressive defeat. How the combination of genetic factors and environmental stressors during adolescence determines adult behavior and how their disturbance results in neuropsychiatric disorders is poorly understood. Niwa et al. found that isolation stress during adolescence, which does not cause any long-lasting changes in wild-type mice, induced significant neurochemical and behavioral alterations in mutant mice expressing a dominant-negative variant of the Disrupted in schizophrenia 1 gene under the control of the prion protein promoter. These deficits could be reversed by a glucocorticoid receptor antagonist.

J. Barik, F. Marti, C. Morel, S. P. Fernandez, C. Lanteri, G. Godeheu, J.-P. Tassin, C. Mombereau, P. Faure, F. Tronche, Chronic stress triggers social aversion via glucocorticoid receptor in dopaminoceptive neurons. Science 339, 332–335 (2013). [Abstract] [Full Text]

M. Niwa, H. Jaaro-Peled, S. Tankou, S. Seshadri, T. Hikida, Y. Matsumoto, N. G. Cascella, S.-i. Kano, N. Ozaki, T. Nabeshima, A. Sawa, Adolescent stress–induced epigenetic control of dopaminergic neurons via glucocorticoids. Science 339, 335–339 (2013). [Abstract] [Full Text]

B. S. McEwen, Hormones and the social brain. Science 339, 279–280 (2013). [Abstract] [Full Text]