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Behavioral Neurobiology of Aggression, Alcohol, GABA, and 5-HT

Award Number: R01AA013983
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2003
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Behavioral Neurobiology of Aggression, Alcohol, GABA, and 5-HT - Project Summary Alcohol plays a key role in at least half of all violent assaults, incidents of domestic violence, homicides and murders. However, the neural and behavioral processes underlying the link between alcohol and violence remain poorly understood. This research proposal aims to delineate the neural mechanisms by which alcohol persistently escalates the motivation to commit intense aggressive acts in some individuals. These aims are empirically pursued using a fixed interval (FI) schedule of operant responding which will be reinforced by the opportunity to engage in an aggressive encounter, allowing us to directly quantify aggressive motivation. Here, the role of corticotropin-releasing factor (CRF) in both (1) the motivation to engage in aggressive acts, and (2) the performance of aggressive behaviors will be quantitatively and qualitatively examined. By isolating the motivation to engage in aggression, we will be able to identify the underlying neural mechanisms that relate to subsequent aggressive behaviors. The overarching hypothesis is that escalated aggression, particularly when engendered by repeated exposures to alcohol, is a function of dysregulated CRF-modulated neurocircuits, namely the hypothalamus-ventral tegmental area (VTA) and hypothalamus-dorsal raphé nucleus (DRN) pathways. These circuits may be fundamental to the modulation of emotional processing via dopaminergic and serotonergic systems, respectively. In a specific subset of individuals, we predict that subpopulations of CRF neurons contribute to escalated motivation to seek out aggressive opportunities after alcohol consumption. In the first aim, we plan to fully characterize the enduring nature of alcohol-escalated aggressive motivation as a function of alcohol dose and as it relates to the duration since alcohol consumption. Aim two will use cellular and molecular tools to investigate plasticity in neuropeptidergic mechanisms that contribute to the persistent escalation of aggressive motivation after repeated alcohol intake. This work will reveal changes in overlapping, intersecting or parallel CRF mechanisms that ultimately converge on dopaminergic and serotonergic systems that are critical for emotional processing. We will also use transgenic technology to define the relative importance of CRF-expressing cell populations in hypothalamus-VTA and hypothalamus–DRN circuits. The proposed experimental work portrays highly translational and ethologically valid analyses of species-normative and escalated forms of aggression engendered by alcohol. Novel targets for therapeutic interventions are anticipated based on the results of these studies.


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: 2026 ( Subtotal = -$1 )
2026	2022	TRUSTEES OF TUFTS COLLEGE	80 GEORGE ST	MEDFORD	MA	02155	MIDDLESEX	USA	Alcohol Research Programs	000	20	12/5/2025	NON-COMPETING CONTINUATION	-$1
														Subtotal = -$1

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	TRUSTEES OF TUFTS COLLEGE	169 HOLLAND ST	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	20	6/28/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $364,461 )
2022	2022	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	20	8/2/2022	NON-COMPETING CONTINUATION	$364,461
														Subtotal = $364,461

Issue Date FY: 2021 ( Subtotal = $364,436 )
2021	2021	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	19	7/26/2021	NON-COMPETING CONTINUATION	$364,436
														Subtotal = $364,436

Issue Date FY: 2020 ( Subtotal = $351,738 )
2020	2020	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	18	7/30/2020	NON-COMPETING CONTINUATION	$351,738
														Subtotal = $351,738

Issue Date FY: 2019 ( Subtotal = $351,716 )
2019	2019	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	002	17	7/30/2019	NON-COMPETING CONTINUATION	$351,716
2019	2017	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	15	1/10/2019	NON-COMPETING CONTINUATION	$0
2019	2015	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	001	13	6/24/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $351,716

Issue Date FY: 2018 ( Subtotal = $351,696 )
2018	2018	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	001	16	7/6/2018	COMPETING CONTINUATION	$351,696
2018	2017	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	15	7/3/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $351,696

Issue Date FY: 2017 ( Subtotal = $293,601 )
2017	2017	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	002	15	7/31/2017	NON-COMPETING CONTINUATION	$293,601
2017	2016	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	001	14	12/5/2016	EXTENSION WITH OR WITHOUT FUNDS	$216,423
2017	2015	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	13	12/5/2016	NON-COMPETING CONTINUATION	-$216,423
														Subtotal = $293,601

Issue Date FY: 2016 ( Subtotal = $294,862 )
2016	2016	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	14	7/19/2016	EXTENSION WITH OR WITHOUT FUNDS	$294,862
														Subtotal = $294,862

Issue Date FY: 2015 ( Subtotal = $290,848 )
2015	2015	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	13	7/8/2015	NON-COMPETING CONTINUATION	$290,848
														Subtotal = $290,848

Issue Date FY: 2014 ( Subtotal = $290,971 )
2014	2014	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	12	8/1/2014	NON-COMPETING CONTINUATION	$290,971
														Subtotal = $290,971

Issue Date FY: 2013 ( Subtotal = $321,629 )
2013	2013	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	11	7/26/2013	COMPETING CONTINUATION	$321,629
														Subtotal = $321,629

Issue Date FY: 2012 ( Subtotal = $459,775 )
2012	2012	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	10	7/11/2012	NON-COMPETING CONTINUATION	$459,775
														Subtotal = $459,775

Issue Date FY: 2011 ( Subtotal = $455,017 )
2011	2011	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	9	7/27/2011	NON-COMPETING CONTINUATION	$455,017
														Subtotal = $455,017

Issue Date FY: 2010 ( Subtotal = $572,165 )
2010	2010	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	001	8	7/26/2010	NON-COMPETING CONTINUATION	$490,515
2010	2010	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	7	7/12/2010	SUPPLEMENT FOR EXPANSION	$81,650
														Subtotal = $572,165

Issue Date FY: 2009 ( Subtotal = $457,993 )
2009	2009	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	7	7/22/2009	NON-COMPETING CONTINUATION	$457,993
2009	2009	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	001	7	8/4/2009	NON-COMPETING CONTINUATION	-$457,993
2009	2009	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	002	7	9/28/2009	NON-COMPETING CONTINUATION	$457,993
														Subtotal = $457,993

Issue Date FY: 2008 ( Subtotal = $480,333 )
2008	2008	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	6	7/31/2008	COMPETING CONTINUATION	$480,333
														Subtotal = $480,333

Issue Date FY: 2007 ( Subtotal = $466,083 )
2007	2007	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	5	7/20/2007	NON-COMPETING CONTINUATION	$466,083
														Subtotal = $466,083

Issue Date FY: 2006 ( Subtotal = $466,023 )
2006	2006	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	4	7/19/2006	NON-COMPETING CONTINUATION	$466,023
														Subtotal = $466,023

Issue Date FY: 2005 ( Subtotal = $468,763 )
2005	2005	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	3	7/27/2005	NON-COMPETING CONTINUATION	$468,763
														Subtotal = $468,763

Issue Date FY: 2004 ( Subtotal = $449,843 )
2004	2004	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Alcohol Research Programs	000	2	7/26/2004	NON-COMPETING CONTINUATION	$449,843
														Subtotal = $449,843

Grand Total All Awards = $8,039,856

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Behavioral Neurobiology of Aggression, Alcohol, GABA, and 5-HT

Award Number: R01AA013983

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2003

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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