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9/11 Neuroimmunophysiology of excessive alcohol intake

Award Number: U01AA016651
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: 09/30/2006
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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9/11 Neuroimmunophysiology of excessive alcohol intake - PROJECT SUMMARY/ABSTRACT This Integrative Neuroscience Initiative on Alcoholism (INIA-Neuroimmune, INIA-N) consortium component is for a U01 research project that seeks to determine how neuroimmune signaling molecules and glia contribute to neuronal adaptations in the nucleus accumbens that promote excessive ethanol drinking. Prior work by this INIA- N component identified neuronal adaptations in the nucleus accumbens (NAc) that are associated with excessive alcohol consumption. In particular, we found that ethanol dependence and excessive intake are associated with plasticity in glutamatergic synapses on dopamine D1 receptor-expressing medium spiny neurons (D1MSNs), which comprise a major output pathway of the NAc that is heavily involved in reward-based behaviors. Recently we discovered that, although synaptic excitation is enhanced, the membrane excitability of these neurons not only is suppressed during acute withdrawal from ethanol, but is strongly, inversely, correlated with prior ethanol intake. We will employ mouse behavioral models of chronic and excessive drinking, genetically engineered mice, and brain slice electrophysiology to test the hypothesis that neuroimmune activity contributes to these synaptic and membrane adaptations of D1MSNs. Specific aim 1 will evaluate how neuronal physiology is altered by the cytokine interleukin-33 (IL-33) in an ethanol-dependent manner, and it will use genetically-engineered mice for inducible and conditional deletion of IL-33, or its receptor, from specific cell types (microglia, astrocytes, and/or neurons) to probe the role of this signaling pathway in the escalation of alcohol intake. Specific aim 2 will take a broader approach, using brain slice electrophysiology to ask whether NAc microglia exhibit functional adaptations that correlate with alcohol intake and its associated adaptations in D1MSNs. Specific aim 3 will be collaborative studies on other neuroimmune signaling and regulatory molecules identified by INIA-N investigators’ as playing a role in excessive alcohol intake. Here we will again use brain slice electrophysiology and will determine whether manipulations of these neuroimmune molecules may alter NAc D1MSN physiology to regulate alcohol consumption. These studies will serve the mission of NIAAA by generating new, fundamental knowledge about the effects of alcohol on brain health, and seeks to apply such knowledge to identify new targets for the treatment of excessive alcohol consumption.


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 = $356,625 )
2026	2026	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	000	20	2/6/2026	NON-COMPETING CONTINUATION	$356,625
														Subtotal = $356,625

Issue Date FY: 2025 ( Subtotal = $356,625 )
2025	2025	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	001	19	8/4/2025	NON-COMPETING CONTINUATION	$35,662
2025	2025	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	000	19	3/4/2025	NON-COMPETING CONTINUATION	$320,963
														Subtotal = $356,625

Issue Date FY: 2024 ( Subtotal = $356,625 )
2024	2024	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	001	18	5/21/2024	NON-COMPETING CONTINUATION	$35,662
2024	2024	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	000	18	1/30/2024	NON-COMPETING CONTINUATION	$320,963
														Subtotal = $356,625

Issue Date FY: 2023 ( Subtotal = $356,625 )
2023	2023	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	000	17	2/1/2023	NON-COMPETING CONTINUATION	$356,625
														Subtotal = $356,625

Issue Date FY: 2022 ( Subtotal = $361,348 )
2022	2022	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	001	16	3/22/2022	COMPETING CONTINUATION	$0
2022	2022	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	000	16	2/22/2022	COMPETING CONTINUATION	$356,625
2022	2022	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	002	16	6/15/2022	COMPETING CONTINUATION	$4,723
														Subtotal = $361,348

Issue Date FY: 2015 ( Subtotal = $234,942 )
2015	2015	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Alcohol Research Programs	000	10	8/5/2015	NON-COMPETING CONTINUATION	$234,942
														Subtotal = $234,942

Issue Date FY: 2014 ( Subtotal = $234,942 )
2014	2014	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Alcohol Research Programs	000	9	8/6/2014	NON-COMPETING CONTINUATION	$234,942
														Subtotal = $234,942

Issue Date FY: 2013 ( Subtotal = $225,254 )
2013	2013	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Alcohol Research Programs	000	8	8/7/2013	NON-COMPETING CONTINUATION	$225,254
														Subtotal = $225,254

Issue Date FY: 2012 ( Subtotal = $241,457 )
2012	2012	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Alcohol Research Programs	000	7	8/8/2012	NON-COMPETING CONTINUATION	$241,457
														Subtotal = $241,457

Issue Date FY: 2011 ( Subtotal = $241,457 )
2011	2011	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Alcohol Research Programs	001	6	9/5/2011	COMPETING CONTINUATION	$241,457
2011	2010	UNIVERSITY OF TEXAS AT AUSTIN	COLLEGE OF PHARMACY	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	000	5	9/2/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $241,457

Issue Date FY: 2010 ( Subtotal = $217,759 )
2010	2010	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Alcohol Research Programs	000	5	9/1/2010	NON-COMPETING CONTINUATION	$217,759
														Subtotal = $217,759

Issue Date FY: 2009 ( Subtotal = $219,958 )
2009	2009	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Alcohol Research Programs	000	4	8/18/2009	NON-COMPETING CONTINUATION	$219,958
														Subtotal = $219,958

Issue Date FY: 2008 ( Subtotal = $219,958 )
2008	2008	UNIVERSITY OF TEXAS AT AUSTIN	PO BOX 7159	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	000	3	8/21/2008	NON-COMPETING CONTINUATION	$219,958
														Subtotal = $219,958

Issue Date FY: 2007 ( Subtotal = $219,958 )
2007	2007	UNIVERSITY OF TEXAS AT AUSTIN	PO BOX 7159	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	000	2	8/31/2007	NON-COMPETING CONTINUATION	$219,958
														Subtotal = $219,958

Issue Date FY: 2006 ( Subtotal = $226,526 )
2006	2006	UNIVERSITY OF TEXAS AT AUSTIN	PO BOX 7159	AUSTIN	TX	78712	TRAVIS	USA	Alcohol Research Programs	000	1	9/29/2006	NEW	$226,526
														Subtotal = $226,526

Grand Total All Awards = $4,070,059

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9/11 Neuroimmunophysiology of excessive alcohol intake

Award Number: U01AA016651

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: 09/30/2006

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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