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9/10 Electrophysiology of Alcohol in Extended Amygdala

Award Number: U01AA013498
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/27/2001
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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9/10 Electrophysiology of Alcohol in Extended Amygdala - This is a competitive U01 renewal application under the Integrative Neuroscience Initiative on Alcoholism- Neuroimmune (INIA-N) Consortium (Notice# RFA-AA-20-11/12/13). It is designed to integrate multidisciplinary research projects based on the genomic, cellular, and behavioral neuroadaptations related to excessive alcohol consumption. The overall premise is that excessive alcohol consumption produces changes and adaptations in immune-related pathways that promote and sustain drinking. Mounting evidence indicates that immune-related pathways, including cytokines, are critical to regulating neuronal functions in addiction-related brain regions that underly the excessive drinking and behavioral phenotype associated with Alcohol Use Disorder (AUD). Notably, transcriptomic, and functional results point to interleukin-6 (IL-6) signaling as a strong candidate to test our central hypothesis that cytokines are integral to the neuroadaptations occurring in GABAergic and glutamatergic synapses and play a critical role in excessive drinking and anxiety-like behaviors associated with ethanol dependence and withdrawal. Specifically, we hypothesize that chronic ethanol-induced activation of IL-6 signaling is a major mediator of the central amygdala (CeA) and medial prefrontal cortex (mPFC) synaptic changes that contribute to the escalation of drinking and the associated negative affect. We anticipate that chronic ethanol will produce sex-, brain region- and cell type-specific IL-6 functional changes that subsequently contribute to ethanol dependence-associated behavioral phenotypes and persist (or be exacerbated) with ethanol withdrawal. We will study the IL-6 pathway and its positive and negative regulators (including SOCS3 and IL-10) to unveil potential therapeutic targets to alleviate ethanol-induced inflammation and ameliorate alcohol-related behaviors. In Aim 1 and 2, to induce ethanol dependence, we will use the chronic intermittent ethanol–two-bottle choice (CIE-2BC) paradigm in both male and female mice. We will apply behavioral, biochemical, and electrophysiological approaches to characterize dysregulation of the IL-6 signaling pathways in alcohol-drinking animals. Aim 3 will investigate the behavioral and electrophysiological effects of ethanol- induced neuroimmune responses on physiological functions across species (rodents and rhesus macaques) and cellular and molecular mechanisms of the candidate drugs/neuroimmune signaling that are identified by other INIA-N projects. Thus, we anticipate that our studies will identify cellular mechanisms and neuroimmune targets that contribute to excessive alcohol drinking. Furthermore, our INIA collaborations will promote replicability and translational aspects by testing our key targets in multiple species using multiple complementary approaches to bridge alcohol basic research with the human condition. The key personnel have extensive publications within their areas of expertise and ongoing interactions with many INIA PIs that are invaluable for the completion of the proposed studies. Drs. Roberto and Bajo will be dedicated to the electrophysiology and biochemical studies, and Dr. Roberts to the behavioral 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: 2025 ( Subtotal = $611,980 )
2025	2025	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	24	3/5/2025	NON-COMPETING CONTINUATION	$611,980
														Subtotal = $611,980

Issue Date FY: 2024 ( Subtotal = $668,891 )
2024	2024	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	001	23	5/21/2024	NON-COMPETING CONTINUATION	$78,530
2024	2024	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	23	1/30/2024	NON-COMPETING CONTINUATION	$590,361
														Subtotal = $668,891

Issue Date FY: 2023 ( Subtotal = $655,957 )
2023	2023	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	22	1/30/2023	NON-COMPETING CONTINUATION	$655,957
														Subtotal = $655,957

Issue Date FY: 2022 ( Subtotal = $655,957 )
2022	2022	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	003	21	5/2/2022	COMPETING CONTINUATION	$32,313
2022	2022	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	001	21	3/24/2022	COMPETING CONTINUATION	$0
2022	2022	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	21	2/11/2022	COMPETING CONTINUATION	$655,957
2022	2021	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	002	20	5/2/2022	NON-COMPETING CONTINUATION	-$32,313
														Subtotal = $655,957

Issue Date FY: 2021 ( Subtotal = $669,844 )
2021	2021	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	20	1/15/2021	NON-COMPETING CONTINUATION	$669,844
														Subtotal = $669,844

Issue Date FY: 2020 ( Subtotal = $669,844 )
2020	2020	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	19	1/16/2020	NON-COMPETING CONTINUATION	$669,844
														Subtotal = $669,844

Issue Date FY: 2019 ( Subtotal = $669,844 )
2019	2019	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	18	1/24/2019	NON-COMPETING CONTINUATION	$669,844
														Subtotal = $669,844

Issue Date FY: 2018 ( Subtotal = $669,844 )
2018	2018	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	17	1/18/2018	NON-COMPETING CONTINUATION	$602,860
2018	2018	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	001	17	5/22/2018	NON-COMPETING CONTINUATION	$66,984
														Subtotal = $669,844

Issue Date FY: 2017 ( Subtotal = $669,844 )
2017	2017	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	16	2/1/2017	COMPETING CONTINUATION	$567,917
2017	2017	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	001	16	3/29/2017	SUPPLEMENT FOR EXPANSION	$101,927
2017	2017	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	003	16	4/7/2017	COMPETING CONTINUATION	$32,313
2017	2015	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	002	15	4/7/2017	NON-COMPETING CONTINUATION	-$32,313
														Subtotal = $669,844

Issue Date FY: 2016 ( Subtotal = $219,729 )
2016	2016	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	15	8/25/2016	SUPPLEMENT FOR EXPANSION	$219,729
														Subtotal = $219,729

Issue Date FY: 2015 ( Subtotal = $539,243 )
2015	2015	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	15	8/5/2015	NON-COMPETING CONTINUATION	$539,243
														Subtotal = $539,243

Issue Date FY: 2014 ( Subtotal = $540,191 )
2014	2014	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	14	7/10/2014	NON-COMPETING CONTINUATION	$355,428
2014	2014	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	002	14	7/14/2014	SUPPLEMENT FOR EXPANSION	$0
2014	2014	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	001	14	7/11/2014	SUPPLEMENT FOR EXPANSION	$184,763
														Subtotal = $540,191

Issue Date FY: 2013 ( Subtotal = $340,770 )
2013	2013	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	13	7/30/2013	NON-COMPETING CONTINUATION	$340,770
														Subtotal = $340,770

Issue Date FY: 2012 ( Subtotal = $391,811 )
2012	2012	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	12	7/24/2012	NON-COMPETING CONTINUATION	$391,811
														Subtotal = $391,811

Issue Date FY: 2011 ( Subtotal = $366,420 )
2011	2011	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	11	9/2/2011	COMPETING CONTINUATION	$366,420
														Subtotal = $366,420

Issue Date FY: 2010 ( Subtotal = $322,823 )
2010	2010	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	10	8/9/2010	NON-COMPETING CONTINUATION	$322,823
														Subtotal = $322,823

Issue Date FY: 2009 ( Subtotal = $952,039 )
2009	2009	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Recovery Act Research Support	001	9	9/23/2009	SUPPLEMENT FOR EXPANSION	$635,455
2009	2009	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	9	8/20/2009	NON-COMPETING CONTINUATION	$316,584
														Subtotal = $952,039

Issue Date FY: 2008 ( Subtotal = $307,363 )
2008	2008	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	8	8/26/2008	NON-COMPETING CONTINUATION	$307,363
														Subtotal = $307,363

Issue Date FY: 2007 ( Subtotal = $276,398 )
2007	2007	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	7	8/27/2007	NON-COMPETING CONTINUATION	$276,398
														Subtotal = $276,398

Issue Date FY: 2006 ( Subtotal = $297,837 ) (Continued on the next page)
Grand Total All Awards = $11,598,892

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9/10 Electrophysiology of Alcohol in Extended Amygdala

Award Number: U01AA013498

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/27/2001

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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