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The Journal of Neuroscience, February 15, 2006, 26(7):1971-1978; doi:10.1523/JNEUROSCI.2173-05.2006

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Behavioral/Systems/Cognitive
Forebrain Glucocorticoid Receptors Modulate Anxiety-Associated Locomotor Activation and Adrenal Responsiveness

Maureen P. Boyle,¹ Benedict J. Kolber,¹ Sherri K. Vogt,¹ David F. Wozniak,² and Louis J. Muglia¹

¹Departments of Pediatrics and Molecular Biology and Pharmacology and ²Psychiatry, Washington University, St. Louis, Missouri 63110

Correspondence should be addressed to Dr. Louis J. Muglia, Washington University School of Medicine, 660 South Euclid Avenue, Box 8208, St. Louis, MO 63110. Email: muglia_l{at}kids.wustl.edu

Stress potently modulates anxiety- and depression-related behaviors. In response to stressors, the hypothalamic-pituitary-adrenal (HPA) axis is activated, resulting in the release of glucocorticoids from the adrenal cortex. These hormones act peripherally to restore homeostasis but also feed back to the CNS to control the intensity and duration of the stress response. Glucocorticoids act in limbic areas of the CNS to mediate the psychological and behavioral effects of stress. In this study, we investigate the effect of forebrain-specific disruption of the glucocorticoid receptor (GR) on stress- and anxiety-related behaviors. We demonstrate that mice with disruption of forebrain GR show alterations in stress-induced locomotor activation in a number of anxiety-related behavioral paradigms. These changes are associated with alterations in stress-induced HPA axis activation and, importantly, are not attenuated by chronic treatment with the tricyclic antidepressant imipramine. These data demonstrate the importance of forebrain GR in regulation of physiological and behavioral stress reactivity and suggest that distinct pathways regulate despair- and anxiety-related behaviors.

Key words: glucocorticoid receptor; HPA axis; anxiety; knock-out mice; behavior; forebrain

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Received May 28, 2005; revised Jan. 4, 2006; accepted Jan. 7, 2006.

Correspondence should be addressed to Dr. Louis J. Muglia, Washington University School of Medicine, 660 South Euclid Avenue, Box 8208, St. Louis, MO 63110. Email: muglia_l{at}kids.wustl.edu

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