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Pituitary Adenylate Cyclase-Activating Peptide (PACAP) Action on Neurotransmission in the Extended Amygdala During Alcohol-Abstinence

Award Number: R01AA032581
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: 08/20/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2031

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Pituitary Adenylate Cyclase-Activating Peptide (PACAP) Action on Neurotransmission in the Extended Amygdala During Alcohol-Abstinence - PROJECT SUMMARY/ABSTRACT Abstinence from alcohol use induces a negative affective state that can lead to maladaptive responses to stress and relapse. Preclinical studies identify neurocircuits and peptide targets that regulate negative affect during abstinence. As the field develops a deeper understanding of the circuitries participating in addiction and negative affect, the next step is to understand how communication in these circuits is modulated differentially in females and males, particularly at the neuropeptide level. Given males and females exhibit different phenotypes (e.g., telescoping effect seen in females), investigating neuropeptide targets in males and females could lead to more effective treatments in alcohol use disorder. The bed nucleus of the stria terminalis (BNST) is a fundamental component of abstinence-relevant neurocircuitry that modulates stress and alcohol-related behavior differentially in males and females in a neuropeptide-dependent manner. The BNST receives pituitary adenylate cyclase-activating peptide (PACAP), a neuropeptide that clinical studies demonstrate has higher alcohol-related dysregulation in females relative to males. Preclinical studies demonstrate that in the BNST, there are differences in PACAP expression in naïve and post ethanol exposure in males and females, and PACAP induces anxiety and increases alcohol intake in males. However, the role of PACAP+ projections on BNST neurotransmission or if there are differences in males and females in abstinence are unknown. The parabrachial nucleus (PBN) is the primary source of PACAP in the BNST. Our published and preliminary data demonstrate that the PBN modulates anxiety in in alcohol abstinence and alcohol naïve conditions and thereby, may underlie the anxiogenic effect of PACAP in the BNST, in part through dysregulated neurotransmission. The research aims to identify how PACAP+ projections from the PBN to the BNST contribute to anxiety and stress response during abstinence and post-abstinence drinking in males and females, Aim 1 will focus on determining how these projections modulate neurotransmission in abstinence after stress and in stress-naïve conditions, with experiments examining the role of PBN(PACAP) via ex vivo recordings of neuronal activity. Aim 2 will investigate how PBN(PACAP) projections modulate in vivo neurotransmission, stress, and anxiety-like behavior during abstinence. Aim 3 will examine the effectiveness of inhibiting PBN(PACAP) projections during and after abstinence in preventing stress-induced alcohol intake and dysregulated neurotransmission in vivo. By exploring the role of PBN(PACAP) projections on stress, anxiety, alcohol intake and neurotransmission in the BNST, the study aims to inform how inhibiting PACAP-associated systems can alleviate dysregulated neurotransmission and anxiety in alcohol-use disorder.


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 = $536,524 )
2026	2026	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Alcohol Research Programs	000	1	8/21/2026	NEW	$536,524
														Subtotal = $536,524

Grand Total All Awards = $536,524

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Pituitary Adenylate Cyclase-Activating Peptide (PACAP) Action on Neurotransmission in the Extended Amygdala During Alcohol-Abstinence

Award Number: R01AA032581

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: 08/20/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2031

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