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Sex-specific effects of infant trauma on adult alcohol drinking: Role of amygdala intercalated neurons

Award Number: R21AA028602
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary Childhood trauma confers vulnerability to comorbid PTSD/AUD, particularly in female patients. Because the neural substrates mediating vulnerability to PTSD and AUD may be similar, elucidating these common mechanisms may provide the foundation for novel treatment options for both. Infant trauma is a powerful, construct-valid model of PTSD and AUD. Trauma-exposed animals show potentiated fear learning, resistance to extinction, and increased alcohol drinking as adults and there is an enhanced vulnerability to these effects in females. This proposal explores the novel hypothesis that infant trauma produces enduring upregulation in MOR expression in amygdala intercalated neurons, ultimately disinhibiting neurons of the central amygdala. Our experiments will test this hypothesis through completion of three primary specific aims. In male and female mice, we will 1) determine whether MOR mRNA expression is increased in amygdala intercalated neurons following infant trauma 2) identify novel molecular targets in the ITC that are regulated by stress and alcohol, and 3) demonstrate a causal role for intercalated cells MORs in mediating the effects of infant trauma on alcohol drinking. Infant trauma will be modeled by delivering 15 footshocks on postnatal day 17. Alcohol drinking will be assessed in a two-bottle choice, drinking in the dark paradigm. Collectively, completion of these aims will provide support for a mechanism by which early life adversity may increase sensitivity to stressors and increase drinking in adulthood. Our work will also further validate a model of traumatic stress and sex- dependent effects on alcohol drinking.


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: 2022 ( Subtotal = $169,322 )
2022	2022	MIAMI UNIVERSITY	501 E HIGH ST	OXFORD	OH	45056	BUTLER	USA	Alcohol Research Programs	000	2	8/19/2022	NON-COMPETING CONTINUATION	$169,322
														Subtotal = $169,322

Issue Date FY: 2021 ( Subtotal = $198,571 )
2021	2021	MIAMI UNIVERSITY	501 E HIGH ST	OXFORD	OH	45056	BUTLER	USA	Alcohol Research Programs	000	1	9/20/2021	NEW	$198,571
														Subtotal = $198,571

Grand Total All Awards = $367,893

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Sex-specific effects of infant trauma on adult alcohol drinking: Role of amygdala intercalated neurons

Award Number: R21AA028602

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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