Tuesday, April 1, 2025 4/1/2025

8/11 Targeting Anti-inflammatory Gene Expression in Binge-like Drinking

Award Number: U01AA013519
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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8/11 Targeting Anti-inflammatory Gene Expression in Binge-like Drinking - Project Summary High Drinking in the Dark (HDID) mice have been selectively bred to drink to intoxication. HDID mice are genetically distinct and represent a unique genotype for drug screening. Many of the compounds that reduce drinking in other strains (e.g., C57BL/6J) do not reduce drinking in HDID mice, and also fail to reduce drinking in humans. Many INIA-Neuroimmune studies have found that alcohol alters inflammatory signaling. We employed a rigorous approach for testing whether several compounds targeting immune signaling could reduce binge-like drinking in HDID mice. To date, 14 out of 28 compounds tested in HDID mice were able to reduce binge-like drinking in HDID mice. Apremilast, a phosphodiesterase type 4 inhibitor and our most promising clinical target, and other compounds that reduced binge-like drinking have one thing in common - they increase anti-inflammatory (e.g. IL-10) signaling. These results offer a broadly unifying hypothesis for more mechanistic experiments to investigate how the balance of pro- and anti-inflammatory signaling regulates binge-like drinking in HDID mice. Here, we study this mechanism in the context of initiation of binge-like drinking, and determine whether this framework holds true under chronic binge drinking conditions. An overarching goal of this proposal is to identify and target anti-inflammatory signatures to reduce drinking and restore alcohol-induced changes in anti- and pro-inflammatory signaling in the brain. Specfic Aim 1 tests whether specific inflammatory signaling pathways contribute to binge-like drinking in iHDID mice using a combination of complementary molecular, genetic, pharmacological, and behavioral approaches in collaboration with INIA-N PIs Roberto, Mangieri, Bilbo, and Lasek. Specific Aim 2 tests whether chronic binge- like drinking is accompanied and/or regulated by anti-inflammatory gene expression in iHDID-1 mice. Aim 2 will employ informatics approaches to identify compounds for behavioral and molecular studies in collaboration with INIA-N PI Mayfield. This project also collaborates with INIA-Stress PIs Vazey/Mooreman and Becker/Lopez to test the effects of promising compounds on other behaviors, and shares the HDID and HS/Npt mouse lines as unique resources developed and maintained under this award with investigators nationwide.


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 = $339,512 )
2025	2025	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	000	24	3/5/2025	NON-COMPETING CONTINUATION	$339,512
														Subtotal = $339,512

Issue Date FY: 2024 ( Subtotal = $377,237 )
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	000	23	1/23/2024	NON-COMPETING CONTINUATION	$339,512
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	001	23	5/21/2024	NON-COMPETING CONTINUATION	$37,725
														Subtotal = $377,237

Issue Date FY: 2023 ( Subtotal = $377,237 )
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	000	22	1/30/2023	NON-COMPETING CONTINUATION	$377,237
														Subtotal = $377,237

Issue Date FY: 2022 ( Subtotal = $377,237 )
2022	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	001	21	3/11/2022	COMPETING CONTINUATION	$377,237
2022	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	002	21	3/22/2022	COMPETING CONTINUATION	$0
2022	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	003	20	7/21/2022	NON-COMPETING CONTINUATION	$0
2022	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	000	20	3/3/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $377,237

Issue Date FY: 2021 ( Subtotal = $432,843 )
2021	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	000	20	2/11/2021	NON-COMPETING CONTINUATION	$432,843
														Subtotal = $432,843

Issue Date FY: 2020 ( Subtotal = $432,843 )
2020	2020	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	001	19	5/28/2020	NON-COMPETING CONTINUATION	$0
2020	2020	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	000	19	1/24/2020	NON-COMPETING CONTINUATION	$432,843
														Subtotal = $432,843

Issue Date FY: 2019 ( Subtotal = $436,019 )
2019	2019	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	000	18	1/24/2019	NON-COMPETING CONTINUATION	$436,019
														Subtotal = $436,019

Issue Date FY: 2018 ( Subtotal = $436,019 )
2018	2018	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	003	17	1/18/2018	NON-COMPETING CONTINUATION	$392,418
2018	2018	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	004	17	5/23/2018	NON-COMPETING CONTINUATION	$43,601
2018	2017	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	001	16	11/29/2017	COMPETING CONTINUATION	$448,500
2018	2017	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	000	16	11/16/2017	COMPETING CONTINUATION	-$448,500
2018	2016	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	002	15	12/20/2017	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $436,019

Issue Date FY: 2017 ( Subtotal = $448,500 )
2017	2017	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	000	16	2/20/2017	COMPETING CONTINUATION	$448,500
2017	2015	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	001	15	4/7/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $448,500

Issue Date FY: 2016 ( Subtotal = $178,352 )
2016	2016	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	001	15	8/26/2016	SUPPLEMENT FOR EXPANSION	$178,352
2016	2015	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	972013098	MULTNOMAH	USA	Alcohol Research Programs	000	15	8/25/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $178,352

Issue Date FY: 2015 ( Subtotal = $428,068 )
2015	2015	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	000	15	8/5/2015	NON-COMPETING CONTINUATION	$428,068
														Subtotal = $428,068

Issue Date FY: 2014 ( Subtotal = $427,992 )
2014	2014	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	000	14	8/4/2014	NON-COMPETING CONTINUATION	$427,992
														Subtotal = $427,992

Issue Date FY: 2013 ( Subtotal = $410,270 )
2013	2013	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	000	13	8/12/2013	NON-COMPETING CONTINUATION	$410,270
														Subtotal = $410,270

Issue Date FY: 2012 ( Subtotal = $441,074 )
2012	2012	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	000	12	7/27/2012	NON-COMPETING CONTINUATION	$441,074
														Subtotal = $441,074

Issue Date FY: 2011 ( Subtotal = $441,000 )
2011	2011	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	000	11	9/2/2011	COMPETING CONTINUATION	$441,000
2011	2009	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97201	MULTNOMAH	USA	Trans-NIH Recovery Act Research Support	001	9	9/28/2011	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $441,000

Issue Date FY: 2010 ( Subtotal = $410,480 )
2010	2010	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	001	10	9/1/2010	NON-COMPETING CONTINUATION	$410,480
2010	2009	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97201	MULTNOMAH	USA	Trans-NIH Recovery Act Research Support	000	9	6/16/2010	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $410,480

Issue Date FY: 2009 ( Subtotal = $844,505 )
2009	2009	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Trans-NIH Recovery Act Research Support	001	9	9/28/2009	SUPPLEMENT FOR EXPANSION	$441,958
2009	2009	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Alcohol Research Programs	000	9	8/24/2009	NON-COMPETING CONTINUATION	$402,547
														Subtotal = $844,505

Issue Date FY: 2008 ( Subtotal = $390,826 )
2008	2008	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97201	MULTNOMAH	USA	Alcohol Research Programs	000	8	8/29/2008	NON-COMPETING CONTINUATION	$390,826
														Subtotal = $390,826

Grand Total All Awards = $10,042,942

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8/11 Targeting Anti-inflammatory Gene Expression in Binge-like Drinking

Award Number: U01AA013519

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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