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Single-Cell Dissection of Ensembles and Cell Types Mediating Opioid Action in the Rodent Brain

Award Number: R01DA054584
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Single-Cell Dissection of Ensembles and Cell Types Mediating Opioid Action in the Rodent Brain - Substance use disorder (SUD) is a debilitating condition characterized by compulsive use of a substance, in spite of the subjective recognition of the drawbacks associated with its use. Chronic use of the substance leads to the development of withdrawal and dependence, hindering intentional controls over its use. Among all substances, opioids are among the ones that pose the greatest negative impact on our society. Animal and human studies have implicated several brain regions involved in opioid use disorder (OUD), in particular various components of the dopamine system. Major dopamine-containing neurons are clustered in regions of the midbrain called the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). Classically, their activities correlate with valence, e.g., promoting approach behavior to rewarding stimuli. Upstream of them, two major circuits are involved: one including the nucleus accumbens projecting onto the VTA, and the other including the dorsal striatum projecting onto the SNc. The scope of this study is thus to conduct in-depth transcriptomics across the cells of these two circuits to dissect genes, pathways, and cell types mediating opioid action in the mouse brain. We will use these data to predict driver genes, regulatory regions, pathways, and cell types involved in the emergence of opioid addiction behaviors. Finally, to test the causal role of these predicted drivers, we will use opioid self-administration, a classical paradigm used in the field of addiction. By combining a rich set of behavioral protocols with state-of-the-art transcriptomics, epigenomics, and computational data analysis, we aim to obtain multi-modal data with an unprecedented level of single-cell resolution for identifying genes, pathways, and cell types affected in mouse models of OUD.


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 = $616,630 )
2025	2025	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	4	2/28/2025	NON-COMPETING CONTINUATION	$554,968
2025	2025	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	4	4/10/2025	NON-COMPETING CONTINUATION	$61,662
														Subtotal = $616,630

Issue Date FY: 2024 ( Subtotal = $616,630 )
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	3	2/13/2024	NON-COMPETING CONTINUATION	$554,968
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	3	4/26/2024	NON-COMPETING CONTINUATION	$61,662
														Subtotal = $616,630

Issue Date FY: 2023 ( Subtotal = $616,630 )
2023	2023	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	2	2/9/2023	NON-COMPETING CONTINUATION	$616,630
														Subtotal = $616,630

Issue Date FY: 2022 ( Subtotal = $616,630 )
2022	2022	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	1	5/25/2022	NEW	$616,630
														Subtotal = $616,630

Grand Total All Awards = $2,466,520

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Single-Cell Dissection of Ensembles and Cell Types Mediating Opioid Action in the Rodent Brain

Award Number: R01DA054584

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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