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Mesocortical neuromodulation in punishment-resistant alcohol drinking

Award Number: R01AA030115
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: 06/25/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Mesocortical neuromodulation in punishment-resistant alcohol drinking - Project Summary Long-standing hypotheses have posited a critical role for dysregulated dopaminergic neuromodulation of prefrontal cortex in the development of alcohol use disorder (AUD). Despite intense interest in the mesocortical dopamine system, technical challenges have precluded direct, temporally resolved observation of dopamine release patterns in the prefrontal cortex until recently. Accordingly, questions regarding the basic function of mesocortical dopamine as well as its role in AUD have been notoriously difficult to address. Here we propose to use a recently developed genetically-encoded fluorescent dopamine sensor, which allows for direct assessment of dopamine dynamics in vivo with unprecedented specificity and temporal resolution, to dissect dopamine release patterns in the medial prefrontal cortex (mPFC) associated with alcohol self-administration behaviors. In male and female mice, we will first test the responsiveness of dopamine innervation of mPFC to a range of stimuli including alcohol to determine its contribution to basic behavioral processes. Next we will assess how these release patterns evolve during initiation of alcohol self-administration and repeated alcohol exposure to determine if deficits in this system are associated with the emergence of heightened alcohol drinking and seeking. Finally, we will mechanistically investigate mesocortical control of alcohol drinking behaviors by manipulating the activity of this system in vivo and determine alcohol’s direct actions on presynaptic dopamine terminals in the mPFC using ex vivo imaging. Completion of this proposal will provide unprecedented insight and understanding as to the contribution of dysregulated cortical neuromodulation in AUD-relevant behaviors.


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 = $401,666 )
2025	2025	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Alcohol Research Programs	000	4	5/8/2025	NON-COMPETING CONTINUATION	$401,666
														Subtotal = $401,666

Issue Date FY: 2024 ( Subtotal = $410,095 )
2024	2024	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Alcohol Research Programs	001	3	5/10/2024	NON-COMPETING CONTINUATION	$41,010
2024	2024	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Alcohol Research Programs	000	3	3/21/2024	NON-COMPETING CONTINUATION	$369,085
														Subtotal = $410,095

Issue Date FY: 2023 ( Subtotal = $418,526 )
2023	2023	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Alcohol Research Programs	000	2	3/29/2023	NON-COMPETING CONTINUATION	$418,526
														Subtotal = $418,526

Issue Date FY: 2022 ( Subtotal = $426,959 )
2022	2022	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Alcohol Research Programs	000	1	6/20/2022	NEW	$444,030
2022	2022	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Alcohol Research Programs	001	1	7/8/2022	NEW	-$17,071
														Subtotal = $426,959

Grand Total All Awards = $1,657,246

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Mesocortical neuromodulation in punishment-resistant alcohol drinking

Award Number: R01AA030115

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: 06/25/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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