Tuesday, April 1, 2025 4/1/2025

1/8: INIA Stress and Chronic Alcohol Interactions: Role of Dynorphin/KOR and Oxytocin Systems in Stress-Enhanced Alcohol Drinking, Relapse, and Impaired Behavioral Flexibility

Award Number: U01AA014095
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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1/8: INIA Stress and Chronic Alcohol Interactions: Role of Dynorphin/KOR and Oxytocin Systems in Stress-Enhanced Alcohol Drinking, Relapse, and Impaired Behavioral Flexibility - PROJECT SUMMARY Stress is known to be a significant factor in triggering relapse, promoting heavy alcohol (ethanol) consumption, and producing adaptations that reduce behavioral flexibility, thereby compromising control over alcohol drinking and elevating susceptibility to relapse. Unfortunately, mechanisms and neurocircuitry underlying the complex interaction between stress and alcohol drinking are not well understood. As part of the INIAstress Consortium, we developed a mouse model in which repeated brief forced swim stress (FSS) exposure interacts with chronic intermittent ethanol (CIE) exposure to selectively enhance alcohol drinking in dependent (CIE-exposed) mice. During the current funding period we established a role for the pro-stress neuropeptide dynorphin/kappa opioid receptor (DYN/KOR) system in stress-enhanced alcohol drinking. At the same time, we used operant conditioning procedures to demonstrate that the anti-stress neuropeptide oxytocin (OT) reduced alcohol self- administration and stress-induced relapse-like behavior. This research project focuses on the role of DYN/KOR and OT systems within stress-relevant circuits in models demonstrating the ability of stress to interact with chronic alcohol in promoting escalation of alcohol drinking, enhanced relapse-like behavior, and impaired behavioral flexibility. The project will employ two stressors (forced swim stress (FSS) and predator odor (TMT) exposure), two models of stress-alcohol interactions (CIE-FSS Drinking and stress (TMT)-induced operant alcohol relapse seeking/drinking), and two measures of behavioral (in)flexibility (alcohol-biased choice behavior and persistence of alcohol drinking despite aversion). Building on our previous work demonstrating an important role for DYN/KOR activity in the central amygdala (CeA) and pilot data showing strong DYN input to the CeA from the insular cortex (a stress and alcohol sensitive cortical area), studies will examine the role of DYN/KOR signaling in insular cortical (IC) projections to the CeA (IC-CeADYN pathway). Other pilot data suggest that the stress-buffering effects of OT may be mediated by signaling in the CeA. Thus, studies will examine OT activity in hypothalamic (PVN) projections to the CeA (PVN-CeAOT pathway). Further, studies will examine the potential unique interactive effects of the DYN/KOR and OT systems in the PVN on behavioral consequences of stress-alcohol interactions. The general experimental strategy will entail utilizing transgenic mice and pharmacological, chemogenetic, and CRISPR/Cas9 approaches to target manipulation of these neuropeptides in specific neurons within these specific neurocircuits. Collectively, these studies focus on adaptations in pro-stress (DYN/KOR) and anti-stress (OT) systems within stress-relevant neurocircuits using different stressors and different drinking models, thereby directly interfacing with the overall thematic framework of the consortium. The ultimate goal is to gain new knowledge that will inform development of more effective interventions for treating stress-related excessive alcohol drinking and relapse.


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: 2025 ( Subtotal = $407,700 )
2025	2025	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	000	23	3/20/2025	NON-COMPETING CONTINUATION	$407,700
														Subtotal = $407,700

Issue Date FY: 2024 ( Subtotal = $453,000 )
2024	2024	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	000	22	1/26/2024	NON-COMPETING CONTINUATION	$407,700
2024	2024	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	001	22	5/17/2024	NON-COMPETING CONTINUATION	$45,300
														Subtotal = $453,000

Issue Date FY: 2023 ( Subtotal = $453,000 )
2023	2023	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	000	21	1/31/2023	NON-COMPETING CONTINUATION	$453,000
														Subtotal = $453,000

Issue Date FY: 2022 ( Subtotal = $452,500 )
2022	2022	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	001	20	3/22/2022	COMPETING CONTINUATION	$0
2022	2022	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	000	20	2/16/2022	COMPETING CONTINUATION	$452,500
2022	2022	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	003	20	5/9/2022	COMPETING CONTINUATION	$119,989
2022	2021	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	002	19	5/9/2022	NON-COMPETING CONTINUATION	-$119,989
														Subtotal = $452,500

Issue Date FY: 2021 ( Subtotal = $336,375 )
2021	2021	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	000	19	2/15/2021	NON-COMPETING CONTINUATION	$336,375
														Subtotal = $336,375

Issue Date FY: 2020 ( Subtotal = $336,375 )
2020	2020	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	000	18	1/28/2020	NON-COMPETING CONTINUATION	$336,375
														Subtotal = $336,375

Issue Date FY: 2019 ( Subtotal = $336,375 )
2019	2019	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	000	17	1/24/2019	NON-COMPETING CONTINUATION	$336,375
														Subtotal = $336,375

Issue Date FY: 2018 ( Subtotal = $336,375 )
2018	2018	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	000	16	1/17/2018	NON-COMPETING CONTINUATION	$302,737
2018	2018	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	001	16	5/22/2018	NON-COMPETING CONTINUATION	$33,638
														Subtotal = $336,375

Issue Date FY: 2017 ( Subtotal = $336,375 )
2017	2017	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	002	15	4/26/2017	COMPETING CONTINUATION	$1,046
2017	2017	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	000	15	2/1/2017	COMPETING CONTINUATION	$336,375
2017	2016	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	001	14	4/26/2017	EXTENSION WITH OR WITHOUT FUNDS	-$1,046
														Subtotal = $336,375

Issue Date FY: 2016 ( Subtotal = $293,531 )
2016	2016	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Alcohol Research Programs	000	14	1/28/2016	EXTENSION WITH OR WITHOUT FUNDS	$293,531
														Subtotal = $293,531

Issue Date FY: 2015 ( Subtotal = $284,725 )
2015	2015	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Alcohol Research Programs	000	13	1/28/2015	NON-COMPETING CONTINUATION	$284,725
														Subtotal = $284,725

Issue Date FY: 2014 ( Subtotal = $284,725 )
2014	2014	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Alcohol Research Programs	001	12	5/2/2014	NON-COMPETING CONTINUATION	$20,547
2014	2014	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Alcohol Research Programs	000	12	2/3/2014	NON-COMPETING CONTINUATION	$264,178
														Subtotal = $284,725

Issue Date FY: 2013 ( Subtotal = $272,984 )
2013	2013	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Alcohol Research Programs	000	11	1/23/2013	NON-COMPETING CONTINUATION	$264,178
2013	2013	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Alcohol Research Programs	001	11	6/11/2013	NON-COMPETING CONTINUATION	$8,806
														Subtotal = $272,984

Issue Date FY: 2012 ( Subtotal = $293,531 )
2012	2012	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Alcohol Research Programs	000	10	2/9/2012	COMPETING CONTINUATION	$293,531
														Subtotal = $293,531

Issue Date FY: 2011 ( Subtotal = $414,944 )
2011	2011	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Alcohol Research Programs	000	9	1/24/2011	NON-COMPETING CONTINUATION	$388,540
2011	2011	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Alcohol Research Programs	001	9	7/5/2011	NON-COMPETING CONTINUATION	$26,404
														Subtotal = $414,944

Issue Date FY: 2010 ( Subtotal = $419,448 )
2010	2010	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Alcohol Research Programs	000	8	1/29/2010	NON-COMPETING CONTINUATION	$419,448
														Subtotal = $419,448

Issue Date FY: 2009 ( Subtotal = $943,543 )
2009	2009	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Alcohol Research Programs	002	7	6/15/2009	NON-COMPETING CONTINUATION	$40,742
2009	2009	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Trans-NIH Recovery Act Research Support	003	7	9/30/2009	SUPPLEMENT FOR EXPANSION	$493,255
2009	2009	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Trans-NIH Recovery Act Research Support	004	7	7/15/2009	SUPPLEMENT FOR EXPANSION	$42,869
2009	2009	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Alcohol Research Programs	001	7	2/2/2009	NON-COMPETING CONTINUATION	$366,677
2009	2008	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	000	6	11/11/2008	NON-COMPETING CONTINUATION	$0
														Subtotal = $943,543

Issue Date FY: 2008 ( Subtotal = $398,520 )
2008	2008	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29425	CHARLESTON	USA	Alcohol Research Programs	000	6	1/31/2008	NON-COMPETING CONTINUATION	$398,520
														Subtotal = $398,520

Grand Total All Awards = $8,270,591

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1/8: INIA Stress and Chronic Alcohol Interactions: Role of Dynorphin/KOR and Oxytocin Systems in Stress-Enhanced Alcohol Drinking, Relapse, and Impaired Behavioral Flexibility

Award Number: U01AA014095

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

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