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Cortical-noradrenaline signaling in alcohol behavioral engagement

Award Number: R00AA030828
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: 09/03/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Cortical-noradrenaline signaling in alcohol behavioral engagement - Project Summary The overarching hypothesis of this proposal is that locus coeruleus–cortical circuits regulate behavioral engagement during alcohol-directed responding, and that this engagement is enhanced following protracted alcohol drinking. Alcohol use disorder is characterized not only by excessive intake, but also by maladaptive behavioral engagement with alcohol-related actions despite negative consequences. Cortical regions within the salience network, including the anterior cingulate cortex (ACC) and anterior insula (aINS), are strongly positioned to regulate these processes because of their roles in attention, motivation, and interoception. However, the neural circuit mechanisms through which these cortical regions coordinate alcohol-directed behavior remain poorly understood. To address this gap, the R00 phase of this award will use high-density silicon probes to record neural activity within the ACC and aINS during performance of a 5-choice serial reaction time task (5-CSRTT) adapted for alcohol reinforcement. This behavioral model, developed by the principal investigator, provides a platform for measuring alcohol-directed engagement through task-relevant measures of attention, impulsivity, and motivation. By recording neural ensemble activity during key behavioral timepoints, these studies will define how ACC and aINS activity patterns encode alcohol-related behavioral engagement and how these patterns are altered following a history of protracted alcohol drinking. Further, this award will examine the functional contribution of noradrenergic signaling to alcohol-directed engagement. The locus coeruleus provides the primary source of cortical norepinephrine and is a critical regulator of arousal, attention, behavioral flexibility, and stress-related responding. Using chemogenetic manipulation of noradrenergic signaling during alcohol-directed 5-CSRTT performance, these experiments will determine whether locus coeruleus–cortical input causally modulates behavioral engagement for alcohol and associated cortical ensemble activity. Together, these approaches will identify both the neural correlates and functional mechanisms through which noradrenergic cortical circuits contribute to maladaptive alcohol engagement. The proposed studies will provide important groundwork for future R01 applications focused on projection-specific circuit inhibition, cell-type-specific modulation of cortical alcohol-responsive ensembles, and therapeutic strategies aimed at reducing maladaptive alcohol-seeking and alcohol-engagement behaviors. By combining a novel alcohol-directed behavioral model with in vivo electrophysiology and circuit-based manipulation, this award will establish a mechanistic framework for understanding how cortical contribute to problem alcohol use. Completion of the R00 phase will provide the candidate with the experimental foundation, preliminary data, and technical expertise necessary to establish an independent research program within the alcohol field and contribute to the development of future interventions for 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 = $249,000 )
2026	2026	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Alcohol Research Programs	000	3	9/7/2026	SUPPLEMENT FOR EXPANSION	$249,000
														Subtotal = $249,000

Grand Total All Awards = $249,000

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Cortical-noradrenaline signaling in alcohol behavioral engagement

Award Number: R00AA030828

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: 09/03/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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