Depression, a destructive psychiatric disorder, is estimated to affect 18 million people per year. Anxiety and memory changes associated with depression have been connected to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, the endocrine stress response. HPA axis and behavioral changes can be either positive (i.e., increasing HPA drive and behavior) or negative (i.e., decreasing drive) in a state of chronic stress. It has been postulated that the various effects of stress on anxiety and memory can be at least partially accounted for by the altered activity of glucocorticoid receptors (GR). In accord with this hypothesis, evidence from pharmacological and genetic studies has demonstrated the capacity of differing amounts of GR activity in different brain areas to produce contrasting changes on anxiety and memory. Specifically, GRs in the hippocampus and hypothalamus are involved in decreasing HPA axis drive while GR in the amygdala is thought to be involved in increasing drive and anxiety. To determine the role of amygdalar GR in depression-related changes and HPA axis modulation, current gene therapy and knockout technology will be used to produce mice with amygdalar disruption of GR. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31MH075250-02
Application #
7262471
Study Section
Special Emphasis Panel (ZRG1-F02A-H (20))
Program Officer
Curvey, Mary F
Project Start
2006-07-03
Project End
2009-07-02
Budget Start
2007-07-03
Budget End
2008-07-02
Support Year
2
Fiscal Year
2007
Total Cost
$26,791
Indirect Cost
Name
Washington University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Kolber, Benedict J; Boyle, Maureen P; Wieczorek, Lindsay et al. (2010) Transient early-life forebrain corticotropin-releasing hormone elevation causes long-lasting anxiogenic and despair-like changes in mice. J Neurosci 30:2571-81
Kolber, Benedict J; Montana, Michael C; Carrasquillo, Yarimar et al. (2010) Activation of metabotropic glutamate receptor 5 in the amygdala modulates pain-like behavior. J Neurosci 30:8203-13
Kolber, Benedict J; Muglia, Louis J (2009) Defining brain region-specific glucocorticoid action during stress by conditional gene disruption in mice. Brain Res 1293:85-90
Kolber, Benedict J; Wieczorek, Lindsay; Muglia, Louis J (2008) Hypothalamic-pituitary-adrenal axis dysregulation and behavioral analysis of mouse mutants with altered glucocorticoid or mineralocorticoid receptor function. Stress 11:321-38
Kolber, Benedict J; Roberts, Marie S; Howell, Maureen P et al. (2008) Central amygdala glucocorticoid receptor action promotes fear-associated CRH activation and conditioning. Proc Natl Acad Sci U S A 105:12004-9