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Prenatal Alcohol and Anxiety: An Ontogenetic Role for CRF

Award Number: R01AA028566
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/15/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Prenatal Alcohol and Anxiety: An Ontogenetic Role for CRF - Abstract Alcohol drinking and alcohol abuse during pregnancy is surprisingly high which can lead to a spectrum of deficits in offspring termed Fetal Alcohol Spectrum Disorders. One of the most common consequences of prenatal alcohol exposure (PAE) is the emergence of anxiety disorders that are apparent in childhood and persist through adulthood. Coincident and highly associated with anxiety is the prevalence of alcohol abuse in individuals with PAE. Importantly, these observations are evident even following exposure to moderate levels of ethanol – a common pattern of alcohol consumption in pregnancy. Despite compelling epidemiological data, the neurobiological mechanisms underlying moderate PAE-induced anxiety are not well understood. The actions of corticotropin-releasing factor (CRF) through its cognate receptor, CRF1R, are involved in alcohol exposure-induced anxiety and alcohol preference in adult males, and their expression is altered by PAE in anxiety-related brain structures. However, the developmental time-course of CRF1R function and how its function is altered by PAE across ontogeny is unknown. We have recently characterized a model of moderate PAE using a single exposure to vaporized ethanol on gestational day (G) 12, a developmental epoch during which the amygdala begins to appear, that produces increased anxiety-like behaviors in adolescent male offspring and affects emotional processing in adult males, with no apparent effects in females. Based on this, we hypothesize that G12 PAE reduces CRF1R function through ontogeny, which contributes to the biphasic anxiety phenotype and results in alterations in acute alcohol and CRF1R interactions. To test our hypothesis, Aim 1 will determine the developmental time-course of CRF1R function within the central amygdala and its relation to anxiety-like behaviors. Aim 2 will examine the impact of moderate G12 PAE on alterations to CRF1R function within the central amygdala across development and into adulthood, as it contributes to PAE-induced alterations in anxiety-like behavior. Finally, Aim 3 will test the effect of moderate G12 PAE on acute ethanol- CRF1R interactions within the central amygdala and how CRF1R contribute to ethanol intake across ontogeny. These innovative studies will test novel and unique hypotheses surrounding the long-term effects of moderate PAE and describe neural mechanisms specific to deficits in anxiety-like behaviors and its association with elevated ethanol intake in an age- and sex-specific manner.


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 = $411,209 )
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	4400 VESTAL PKWY E	BINGHAMTON	NY	13902	BROOME	USA	Alcohol Research Programs	002	4	5/22/2024	NON-COMPETING CONTINUATION	$34,709
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	4400 VESTAL PKWY E	BINGHAMTON	NY	13902	BROOME	USA	Alcohol Research Programs	001	4	4/9/2024	SUPPLEMENT FOR EXPANSION	$64,115
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	4400 VESTAL PKWY E	BINGHAMTON	NY	13902	BROOME	USA	Alcohol Research Programs	000	4	3/29/2024	NON-COMPETING CONTINUATION	$312,385
														Subtotal = $411,209

Issue Date FY: 2023 ( Subtotal = $411,209 )
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	4400 VESTAL PKWY E	BINGHAMTON	NY	13902	BROOME	USA	Alcohol Research Programs	000	3	4/18/2023	NON-COMPETING CONTINUATION	$347,094
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	4400 VESTAL PKWY E	BINGHAMTON	NY	13902	BROOME	USA	Alcohol Research Programs	001	3	4/19/2023	SUPPLEMENT FOR EXPANSION	$64,115
														Subtotal = $411,209

Issue Date FY: 2022 ( Subtotal = $395,932 )
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	4400 VESTAL PKWY E	BINGHAMTON	NY	13902	BROOME	USA	Alcohol Research Programs	000	2	3/29/2022	NON-COMPETING CONTINUATION	$347,094
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	4400 VESTAL PKWY E	BINGHAMTON	NY	13902	BROOME	USA	Alcohol Research Programs	001	2	8/26/2022	SUPPLEMENT FOR EXPANSION	$48,838
														Subtotal = $395,932

Issue Date FY: 2021 ( Subtotal = $347,094 )
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	4400 VESTAL PKWY E	BINGHAMTON	NY	13902	BROOME	USA	Alcohol Research Programs	000	1	6/14/2021	NEW	$347,094
														Subtotal = $347,094

Grand Total All Awards = $1,565,444

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Prenatal Alcohol and Anxiety: An Ontogenetic Role for CRF

Award Number: R01AA028566

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/15/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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