Tuesday, March 3, 2026 3/3/2026

A Novel Role of Interpeduncular Nucleus GLP-1Rs in Fentanyl Reinstatement

Award Number: F31DA058451
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2023
PERIOD OF PERFORMANCE END DATE: 08/11/2025

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A Novel Role of Interpeduncular Nucleus GLP-1Rs in Fentanyl Reinstatement - Project Summary: Fatal opioid overdose is a leading cause of preventable death in the United States, and in 2021 more than 60% of drug overdose deaths were associated with fentanyl and its analogs. While current pharmacological treatments for opioid use disorder are effective, stigma and limited access make these medications underutilized and rates of relapse are still high. Despite the prevalence of illicit fentanyl use, there are very few studies investigating the neurobiological mechanisms underlying fentanyl seeking. Advancing our understanding of the neural circuits underlying fentanyl seeking may facilitate the development of novel treatments for fentanyl use disorder and reduce fentanyl overdose deaths. Recently, we showed that systemic administration of the glucagon-like peptide-1 receptor (GLP-1R) agonist Exendin-4 (Ex-4) attenuates fentanyl reinstatement, a model of relapse. However, the neural mechanisms underlying the suppressive effects of Ex-4 on fentanyl seeking are unclear. Our exciting pilot studies demonstrate that activation of GLP-1Rs in the interpeduncular nucleus (IPN), a brain region known to regulate the mesolimbic dopamine system, is sufficient to attenuate fentanyl-seeking behavior during abstinence in male and female rats. Additionally, we discovered µ opioid receptors and GLP- 1Rs expressed on GABAergic neurons that project from the IPN to the laterodorsal tegmental nucleus (LDTg), a nucleus that sends projections to the VTA and plays an important role in drug seeking and opioid-induced reward. These results highlight a neural circuit that may mediate the suppressive effects of GLP-1R agonists on fentanyl seeking. However, the activity of this circuit during fentanyl-seeking behavior has not been investigated. The goal of this proposal is to determine the impact of acute fentanyl and Ex-4 on neural activity in the GABAergic IPNàLDTg pathway and the relationship between such activity and fentanyl-seeking behavior. To investigate the role of the GABAergic IPNàLDTg projection in fentanyl reinstatement, Aim 1 will use in vivo calcium imaging to characterize the real-time activity of GABAergic IPN projections to the LDTg during fentanyl-seeking behavior. Aim 2 will determine how Ex-4 pharmacotherapy alters calcium activity of GABAergic IPNàLDTg projections to reduce fentanyl seeking. Successful completion of these aims will be an important foundation for future studies investigating the neural basis of fentanyl seeking. Ideally, results from this work will suggest novel therapeutic avenues for fentanyl use disorder. Completion of this fellowship will achieve the training goals of expanding the technical expertise of Ms. Herman in addiction neuroscience and facilitate her career goal of becoming a leading researcher in the neurobiology of substance use disorders.


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 = -$27,884 )
2026	2025	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	3	11/28/2025	NON-COMPETING CONTINUATION	-$27,884
														Subtotal = -$27,884

Issue Date FY: 2025 ( Subtotal = $37,360 )
2025	2025	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	3	6/19/2025	NON-COMPETING CONTINUATION	$37,360
														Subtotal = $37,360

Issue Date FY: 2024 ( Subtotal = $48,974 )
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	2	6/14/2024	NON-COMPETING CONTINUATION	$48,974
														Subtotal = $48,974

Issue Date FY: 2023 ( Subtotal = $47,694 )
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	001	1	7/11/2023	NEW	$0
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	1	3/8/2023	NEW	$47,694
														Subtotal = $47,694

Grand Total All Awards = $106,144

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A Novel Role of Interpeduncular Nucleus GLP-1Rs in Fentanyl Reinstatement

Award Number: F31DA058451

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2023

PERIOD OF PERFORMANCE END DATE: 08/11/2025

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