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CORTICOTROPIN-RELEASING FACTOR/SEROTONERGIC INTERACTIONS

Award Number: R01MH058250
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/1998
PERIOD OF PERFORMANCE END DATE: 06/30/2012

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CORTICOTROPIN-RELEASING FACTOR/SEROTONERGIC INTERACTIONS - DESCRIPTION (provided by applicant): Stress is a major determinant of vulnerability to debilitating psychiatric disorders including, depression, anxiety and substance abuse. The guiding goal of this research is to determine how neuromediators of the stress response interact with neural systems involved in emotion and behavior to produce mental and/or behavioral pathology. Towards this goal, we identified a critical link between stress and affective disorders by demonstrating that corticotropin-releasing factor (CRF), the neuropeptide that orchestrates the stress response, regulates activity of the dorsal raphe (DR)-serotonin (5-HT) system, a neurotransmitter system implicated in psychiatric disorders. Moreover, it was demonstrated that a history of stress changes the nature of CRF regulation of the DR-5-HT system from inhibition to excitation and that this is associated with a shift from active to passive coping behavior. Because passive behavior and inability to make decisions are characteristic and debilitating features of depression, understanding the mechanism of this stress-induced adaptation, the specific conditions that produce it and its sensitivity to pharmacological manipulation will advance our understanding of the pathophysiology of depression and our ability to design appropriate therapeutic strategies. This proposal for a competing renewal integrates diverse technical approaches (PCR, functional neuroanatomy, neurophysiology, microdialysis and behavior) and levels of analyses to achieve the following Specific Aims: 1) Identify molecular and cellular mechanisms underlying stress-induced changes in CRF regulation of the DR-5-HT system that promote a shift from active to passive behavior; 2) Determine whether certain social stressors (e.g., neonatal maternal separation or adult social stress) produce a shift in CRF regulation of the DR and whether this is responsible for depressive-like behavior in these models; and 3) Determine whether the stress-induced adaptations can be reversed by classical or novel antidepressant agents and the mechanisms by which these agents do this. The manner in which individuals respond to stress is a major factor in determining physical and mental health. The proposed studies will advance our knowledge of 1) the biological determinants of different coping styles, 2) mechanisms by which stress results in the debilitating course of depression and 3) how this can be manipulated by pharmacological agents and thereby guide development of novel antidepressants.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2011 ( Subtotal = $517,131 )
2011	2011	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	15	5/24/2011	NON-COMPETING CONTINUATION	$517,131
														Subtotal = $517,131

Issue Date FY: 2010 ( Subtotal = $525,142 )
2010	2010	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	14	6/21/2010	NON-COMPETING CONTINUATION	$525,142
														Subtotal = $525,142

Issue Date FY: 2009 ( Subtotal = $519,861 )
2009	2009	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	13	7/15/2009	NON-COMPETING CONTINUATION	$519,861
														Subtotal = $519,861

Issue Date FY: 2008 ( Subtotal = $607,568 )
2008	2008	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	12	6/3/2008	NON-COMPETING CONTINUATION	$504,850
2008	2008	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	001	12	8/25/2008	SUPPLEMENT FOR EXPANSION	$102,718
														Subtotal = $607,568

Issue Date FY: 2007 ( Subtotal = $538,114 )
2007	2007	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	11	7/30/2007	COMPETING CONTINUATION	$538,114
														Subtotal = $538,114

Issue Date FY: 2006 ( Subtotal = $530,994 )
2006	2006	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	10	12/8/2005	NON-COMPETING CONTINUATION	$530,994
														Subtotal = $530,994

Issue Date FY: 2005 ( Subtotal = $478,946 )
2005	2005	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	9	12/10/2004	NON-COMPETING CONTINUATION	$478,946
														Subtotal = $478,946

Issue Date FY: 2004 ( Subtotal = $465,222 )
2004	2004	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	8	12/15/2003	NON-COMPETING CONTINUATION	$465,222
														Subtotal = $465,222

Issue Date FY: 2003 ( Subtotal = $451,832 )
2003	2003	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	7		NON-COMPETING CONTINUATION	$451,832
														Subtotal = $451,832

Issue Date FY: 2002 ( Subtotal = $475,055 )
2002	2002	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	6	1/16/2002	COMPETING CONTINUATION	$475,055
														Subtotal = $475,055

Issue Date FY: 2001 ( Subtotal = $306,946 )
2001	2001	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	5	3/1/2001	NON-COMPETING CONTINUATION	$306,946
														Subtotal = $306,946

Issue Date FY: 2000 ( Subtotal = $316,354 )
2000	2000	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	4	6/23/2000	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$266,509
2000	2000	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	3	4/13/2000	NON-COMPETING CONTINUATION	$49,845
														Subtotal = $316,354

Issue Date FY: 1999 ( Subtotal = $277,528 )
1999	1999	ALLEGHENY UNIV OF THE HLTH SCIENCES	503 MARTINDALE STREET	PITTSBURGH	PA	15212	ALLEGHENY	USA	Mental Health Research Grants	000	1	9/27/1999	NEW	$1
1999	1999	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	2	9/27/1999	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$277,527
														Subtotal = $277,528

Grand Total All Awards = $6,010,693

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CORTICOTROPIN-RELEASING FACTOR/SEROTONERGIC INTERACTIONS

Award Number: R01MH058250

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/01/1998

PERIOD OF PERFORMANCE END DATE: 06/30/2012

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