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Analysis of subcortical networks that promote aversion-resistant alcohol drinking

Award Number: R15AA027915
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: 09/10/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2024

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Analysis of subcortical networks that promote aversion-resistant alcohol drinking - Project Summary Alcohol use disorder (AUD) is a debilitating and life-long addictive disease with significant public health costs. Individuals suffering from AUD exhibit compulsive alcohol drinking, defined as drinking that is resistant to negative or aversive consequences. While there is a growing recognition in the field of the need for more relevant models of addictive behavior, there is still relatively little known about the neural circuits engaged during compulsive drug seeking. Studies in humans and rats suggest a role for the nucleus accumbens (NAc) core in compulsive-like alcohol drinking. D1-neurons are a subpopulation of neurons in the NAc that project to the midbrain and the ventral pallidum (VP). Activity in D1-neurons is critical in controlling motivated and drug- seeking behaviors. Convergent findings from preclinical models of alcohol dependence and obsessive- compulsive disorder suggest the metabotropic glutamate receptor 5 (mGluR5) may play a role in biasing striatal output toward D1-neurons. Given that alcohol exposure increases mGluR5 expression in the NAc, mGluR5 expression on D1-neurons of the NAc core may serve as a key molecular contributor to compulsive- like alcohol drinking. Our experiments will test this hypothesis through completion of two primary specific aims: We will determine whether 1) mGluR5 expression on NAc core D1-neurons and 2) activity in D1-neuron projections to the VP promote aversion-resistant alcohol drinking in mice. Aversion-resistant drinking will be tested using a drinking in the dark model in which the bitter tastant quinine is added to ethanol. Collectively, completion of these aims will characterize the contribution of mGluR5 on NAc core D1-neuron projections to compulsive alcohol drinking, thereby delineating one of the mechanisms by which alcohol exposure can lead to addictive behavior. Furthermore, we will train undergraduate students in a broad array of modern techniques in behavioral neuroscience, such as chemogenetics, site-specific pharmacology, quantitative real-time PCR, and flow cytometry. These activities will strengthen opportunities for behavioral neuroscience research at Miami University and build institutional knowledge in the use of flow cytometry for neuroscience research.


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: 2024 ( Subtotal = -$3,705 )
2024	2020	MIAMI UNIVERSITY	501 E HIGH ST	OXFORD	OH	45056	BUTLER	USA	Alcohol Research Programs	001	1	8/13/2024	NEW	-$3,705
2024	2020	MIAMI UNIVERSITY	501 E HIGH ST	OXFORD	OH	45056	BUTLER	USA	Alcohol Research Programs	000	1	6/5/2024	NEW	$0
														Subtotal = -$3,705

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	MIAMI UNIVERSITY	501 E HIGH ST	OXFORD	OH	45056	BUTLER	USA	Alcohol Research Programs	000	1	9/15/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $378,136 )
2020	2020	MIAMI UNIVERSITY	501 E HIGH ST	OXFORD	OH	45056	BUTLER	USA	Alcohol Research Programs	000	1	9/9/2020	NEW	$378,136
														Subtotal = $378,136

Grand Total All Awards = $374,431

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Analysis of subcortical networks that promote aversion-resistant alcohol drinking

Award Number: R15AA027915

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: 09/10/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2024

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