Brain CRF systems are important in integrating endocrine, autonomic, and behavioral responses to stress. Preclinical and clinical research suggests an important involvement of CRF systems and the amygdala in mediating symptoms associated with anxiety disorders and depression. CRF containing cell bodies and fibers, as well as the CRF binding protein and CRF receptors are found throughout the amygdala. The investigators have found that the major site of outflow from the amygdala, the central nucleus (CeA), is a brain site where endogenous CRF systems mediate stress-induced behavioral responses. Using site specific administration of a CRF antagonist (CRFa), they demonstrated that CRF receptors in the region of the CeA mediate acute and conditioned freezing behavior. Complementing these studies, they demonstrated that acute stress exposure results in increased amygdala CRF mRNA concentrations. This is the first direct evidence demonstrating that stress activates amygdaloid CRF systems. The overall aim of this proposal is to continue studies examining the role of amygdaloid CRF systems in mediating behavioral responses to stress. The investigators will characterize the effects of stress on the activation of the genes for CRF, its receptor, and its binding protein. The studies will provide important hypotheses regarding the role of CRF systems in mediating pathological anxiety, and other forms of human psychopathology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH040855-09A3
Application #
2033648
Study Section
Special Emphasis Panel (ZMH1-NRB-L (J1))
Project Start
1986-08-01
Project End
2002-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
9
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Psychiatry
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Lee Van Horn, M; Smith, Jessalyn; Fagan, Abigail A et al. (2012) Not quite normal: Consequences of violating the assumption of normality in regression mixture models. Struct Equ Modeling 19:227-249
Qi, C; Roseboom, P H; Nanda, S A et al. (2010) Anxiety-related behavioral inhibition in rats: a model to examine mechanisms underlying the risk to develop stress-related psychopathology. Genes Brain Behav 9:974-84
Nanda, S A; Qi, C; Roseboom, P H et al. (2008) Predator stress induces behavioral inhibition and amygdala somatostatin receptor 2 gene expression. Genes Brain Behav 7:639-48
Bakshi, Vaishali P; Newman, Sarah M; Smith-Roe, Stephanie et al. (2007) Stimulation of lateral septum CRF2 receptors promotes anorexia and stress-like behaviors: functional homology to CRF1 receptors in basolateral amygdala. J Neurosci 27:10568-77
Roseboom, Patrick H; Nanda, Steven A; Bakshi, Vaishali P et al. (2007) Predator threat induces behavioral inhibition, pituitary-adrenal activation and changes in amygdala CRF-binding protein gene expression. Psychoneuroendocrinology 32:44-55
Herringa, Ryan J; Mackenrodt, Daniel B; Barlow, Jon D et al. (2006) Corticotropin-releasing factor (CRF), but not corticosterone, increases basolateral amygdala CRF-binding protein. Brain Res 1083:21-8
Herringa, Ryan J; Roseboom, Patrick H; Kalin, Ned H (2006) Decreased amygdala CRF-binding protein mRNA in post-mortem tissue from male but not female bipolar and schizophrenic subjects. Neuropsychopharmacology 31:1822-31
Jochman, Kimberly A; Newman, Sarah M; Kalin, Ned H et al. (2005) Corticotropin-releasing factor-1 receptors in the basolateral amygdala mediate stress-induced anorexia. Behav Neurosci 119:1448-58
Nanda, Steven A; Roseboom, Patrick H; Nash, George A et al. (2004) Characterization of the human corticotropin-releasing factor2(a) receptor promoter: regulation by glucocorticoids and the cyclic adenosine 5'-monophosphate pathway. Endocrinology 145:5605-15
Herringa, Ryan J; Nanda, Steven A; Hsu, David T et al. (2004) The effects of acute stress on the regulation of central and basolateral amygdala CRF-binding protein gene expression. Brain Res Mol Brain Res 131:17-25

Showing the most recent 10 out of 30 publications