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Corticolimbic Neuroimmune Determinants of Social Stress-Associated Alcohol Drinking

Award Number: K99AA029180
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/05/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2023

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Corticolimbic Neuroimmune Determinants of Social Stress-Associated Alcohol Drinking - PROJECT SUMMARY Social stress is a prevailing factor in the lives of all social species and can motivate the misuse of reinforcing drugs such as alcohol. Individuals that use alcohol to alleviate the negative emotions created by social stress are more likely to develop pathological drinking patterns, which can lead to an alcohol use disorder (AUD). Indeed, an individual’s standing in a social hierarchy (i.e. social rank) is inversely related to alcohol consumption in rodents and non-human primates as well as problematic drinking in humans, highlighting the conserved impact of subordination stress on motivation for alcohol. Social rank also influences how individuals respond to challenges, and social isolation is a particularly profound stressor with increasing human relevance. Our preliminary data identify a previously unknown relationship between mouse social rank and isolation- associated escalated alcohol drinking, where subordinates display a greater magnitude increase in drinking following social isolation compared to dominants. These data suggest that low social rank may be a potent risk factor for developing pathological alcohol drinking patterns. Understanding the neurobiological mechanisms by which social stress experiences engender aberrant alcohol drinking could have important translational implications for AUD. It is becoming increasingly evident that social stress induces microglia-mediated neuroimmune responses in select stress-responsive brain regions, including the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC), which contribute to stress-induced behavioral adaptations. Notably, social isolation-induced escalation of alcohol strongly parallels increases in microglia previously seen following social stress, supporting a potential role for microglia in isolation-induced adaptations in alcohol drinking. Despite the substantial evidence linking social stress and alcohol drinking as well as the impact of social stress on neuroimmune signaling, virtually nothing is known regarding the neuroimmune regulation of circuits underlying social stress-induced behavioral adaptions in alcohol drinking. To fill this gap, this proposal will test the central hypothesis that social stress activates microglia-mediated neuroimmune signaling, which re-shapes amygdalar-cortical circuits underlying escalated alcohol drinking. Preliminary data show that social isolation increases BLA excitability, and the BLA-mPFC circuit regulates alcohol drinking. Dr. Patel will use her new training in advanced circuit imaging and dissection technologies and previous training in cell type specific transcriptomic analysis and ex vivo electrophysiology to 1) dissect the BLA-mPFC contribution to social rank- and isolation-induced alcohol drinking, 2) delineate the impact of BLA substrates on mPFC encoding of alcohol consumption, and 3) identify social stress-induced neuroimmune determinants driving circuit adaptations underlying aberrant alcohol drinking. In executing the proposed experiments and professional development plan, Dr. Patel will be well-positioned to transition to a tenured-track faculty position and establish an independent research program centered around neuroimmune and social stress regulation of circuits in AUD.


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: 2024 ( Subtotal = -$194,898 )
2024	2023	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	001	2	3/5/2024	NON-COMPETING CONTINUATION	-$172,584
2024	2022	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	1	3/5/2024	NEW	-$22,314
														Subtotal = -$194,898

Issue Date FY: 2023 ( Subtotal = $172,584 )
2023	2023	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	001	2	9/6/2023	NON-COMPETING CONTINUATION	$0
2023	2023	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	2	3/30/2023	NON-COMPETING CONTINUATION	$172,584
														Subtotal = $172,584

Issue Date FY: 2022 ( Subtotal = $172,584 )
2022	2022	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Alcohol Research Programs	000	1	4/5/2022	NEW	$172,584
														Subtotal = $172,584

Grand Total All Awards = $150,270

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Corticolimbic Neuroimmune Determinants of Social Stress-Associated Alcohol Drinking

Award Number: K99AA029180

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/05/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2023

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