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The role of prefrontostriatal Pituitary Adenylate Cyclase Activating Polypeptide in excessive and compulsive ethanol drinking

Award Number: F30AA028184
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 08/11/2020
PERIOD OF PERFORMANCE END DATE: 08/10/2024

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The role of prefrontostriatal Pituitary Adenylate Cyclase Activating Polypeptide in excessive and compulsive ethanol drinking - ABSTRACT Approximately 1 in 12 people in the USA abuse or are dependent on alcohol. Alcohol use disorder (AUD) is defined by persistent excessive alcohol intake, and compulsive drinking even in the face of adverse consequences. The neurobiological mechanisms underlying severe alcohol intake, as well as compulsive drinking, are not entirely understood. Increased glutamatergic signaling from prefrontal-striatal projection neurons has been implicated in the escalation of alcohol drinking and compulsive drinking behavior. This project will investigate these projection neurons from the prelimbic cortex (PrL) to the nucleus accumbens core (NAcc) in the context of a novel neuropeptide, Pituitary Adenylate Cyclase Activating Peptide (PACAP), and its receptor PAC1R. Reports in rodents and humans have begun to link the PACAP/PAC1R system to the actions of drugs of abuse, as well as the potentiation of glutamatergic signaling. Our preliminary data localizes this system to PrL to NAcc projection neurons, and suggests the involvement of the PACAP/PAC1R system in excessive drinking behavior. A major gap exists in the field in understanding the role of PACAP in AUD-related behaviors. Therefore, my long-term goal is to understand how this and other neuropeptidergic systems relate to excessive drinking, alcohol dependence, and AUD-related behaviors. The overarching hypothesis of this proposal is that hyperactivity of the PrLPACAP to NAcc neurons increases glutamatergic signaling within the NAcc and leads to excessive and compulsive drinking despite negative consequences. This hypothesis will be tested with an array of cutting-edge techniques including chemogenetic stimulation and inhibition, site-specific pharmacology (Aim 1), and calcium imaging in freely behaving animals (Aim 2). The results of this proposal will greatly add to the field of alcohol research and our understanding of excessive and compulsive 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: 2025 ( Subtotal = -$12,513 )
2025	2023	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Alcohol Research Programs	000	4	6/25/2025	NON-COMPETING CONTINUATION	-$12,513
														Subtotal = -$12,513

Issue Date FY: 2023 ( Subtotal = $52,694 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Alcohol Research Programs	000	4	7/7/2023	NON-COMPETING CONTINUATION	$52,694
														Subtotal = $52,694

Issue Date FY: 2022 ( Subtotal = $51,752 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Alcohol Research Programs	000	3	7/8/2022	NON-COMPETING CONTINUATION	$51,752
														Subtotal = $51,752

Issue Date FY: 2021 ( Subtotal = $51,036 )
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Alcohol Research Programs	000	2	7/22/2021	NON-COMPETING CONTINUATION	$51,036
														Subtotal = $51,036

Issue Date FY: 2020 ( Subtotal = $50,520 )
2020	2020	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Alcohol Research Programs	000	1	8/11/2020	NEW	$50,520
2020	2020	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Alcohol Research Programs	001	1	8/11/2020	NEW	$0
														Subtotal = $50,520

Grand Total All Awards = $193,489

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The role of prefrontostriatal Pituitary Adenylate Cyclase Activating Polypeptide in excessive and compulsive ethanol drinking

Award Number: F30AA028184

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 08/11/2020

PERIOD OF PERFORMANCE END DATE: 08/10/2024

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