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Targeting prefrontostriatal circuits to rescue alcohol-induced behavioral inflexibility

Award Number: F31AA032134
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: 05/01/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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Targeting prefrontostriatal circuits to rescue alcohol-induced behavioral inflexibility - PROJECT SUMMARY The progression of alcohol use disorder (AUD) is characterized by the emergence of inflexible behaviors, such as compulsive drinking, that exacerbate negative outcomes. Substantial evidence links behavioral inflexibility to hypoactivity of the prefrontal cortex, suggesting that deficient cognitive control over behavior drives compulsive drinking. Despite this, current AUD treatments do not address cognitive dysfunction, leaving inflexible behaviors unchecked. Importantly, chemogenetic activation of the dorsomedial prefrontal cortex prevents the progression of compulsive-like drinking in rats. This identifies a promising new avenue for therapeutic development: prefrontocortical disinhibition. Coupled with existing findings, my preliminary data suggest that negative allosteric modulation of α5-subunit containing GABAA receptors (α5GABAAR) may restore behavioral flexibility through disinhibitory action in the prefrontal cortex. To test this, I will implement an operant reversal-learning task to evaluate goal-directed behavior, a core component of behavioral flexibility (Aim 1), and a quinine-challenge to evaluate inflexible, aversion-resistant drinking (Aim 2). Both aims will utilize systemic administration of an α5GABAAR negative allosteric modulator, to model clinical application, and local infusion to directly interrogate the role of prefrontocortical α5GABAARs. Successful completion of these aims will validate prefrontocortical α5 subunit-containing GABAA receptors as a promising, pro-cognitive drug target addressing inflexible behaviors in alcohol use disorder and other neuropsychiatric conditions characterized by cognitive dysfunction. This project expands upon the PI’s existing expertise to provide training on animal behavior and in vivo pharmacological manipulations, which will optimize technical development as an independent researcher examining the cortical circuits driving behavioral flexibility.


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 = $40,624 )
2026	2026	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Alcohol Research Programs	001	1	4/17/2026	NEW	$0
2026	2026	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Alcohol Research Programs	000	1	4/17/2026	NEW	$40,624
														Subtotal = $40,624

Grand Total All Awards = $40,624

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Targeting prefrontostriatal circuits to rescue alcohol-induced behavioral inflexibility

Award Number: F31AA032134

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: 05/01/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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