Investigators have hypothesized that brain corticotropin-releasing factor (CRF) systems play an integrative role in an organism's physiological and behavioral response to a stressor. The role of CRF in hypothalamic-pituitary-adrenal (HPA) axis and autonomic function has been extensively investigated, but the data base linking CRF and stress-related behavior is only suggestive.
The aim of the proposed research is to determine whether CRF brain systems are involved in the behavioral response to a stressor. To achieve this we will alter central CFR systems in the rat and measure several behavioral responses to stress of varied nature and intensity. To alter CRF systems we will administer CRF, CRF antagonist (CRFa), and CRF antiserum intracerebroventricularly (ICV). Stress will consist of varid intensities of footshock or the anticipation of footshock (i.e., conditioned effects of footshock). In this way both the intensity and nature of the stressor will be manipulated. We will also study the role of central CRF systems in the acquisition of associative learning about stressful events. Finally, we will establish whether the behavioral changes due to altered CRF systems are centrally mediated. In all of the experiments multiple dependent measures will be taken. These will be: locomotion, rearing, grooming, freezing, and antinociceptive behavior. Additionally, we will assess HPA activity with plasma levels of ACTH and corticosterone. This research should ascertain the extent to which endogenous brain CRF systems are involved in the mediation of stress-induced behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH040855-05
Application #
3379351
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1986-08-01
Project End
1994-11-30
Budget Start
1991-02-01
Budget End
1991-11-30
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
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

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