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The Genetic and Epigenetic Interplay of Cocaine Addiction: A Cell-Type, Circuitry, and Functional Dissection

Award Number: DP1DA061008
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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The Genetic and Epigenetic Interplay of Cocaine Addiction: A Cell-Type, Circuitry, and Functional Dissection - PROJECT SUMMARY The intricate orchestration of genetic and epigenetic dynamics in neurobiological systems plays a central role in substance use disorders (SUDs), with cocaine use constituting a significant public health concern. This project employs a cutting-edge, interdisciplinary approach to elucidate the epigenetic landscapes and gene regulatory networks activated following cocaine self-administration in a mouse model, as well as to understand how epigenetic variations influence these processes. The project comprises three core objectives at the intersection of genomics, epigenomics, neuroscience, and computational biology. First, we will conduct high-resolution chromatin accessibility and DNA methylation profiling to delineate cell-type and circuit-specific epigenetic configurations post-cocaine self-administration in mice. This analysis aims to uncover granular alterations in the epigenome, illuminating the regulatory pathways implicated in cocaine-induced neural plasticity and behavioral adaptations. Second, we will leverage the Hybrid Mouse Diversity Panel (HMDP), comprising approximately 100 different strains of mice, to investigate variances in epigenetic regulation. Utilizing the HMDP as a mechanistic intermediary, we aim to identify epigenetic variations underlying strain-specific susceptibilities and resistances to cocaine exposure, thus deepening our understanding of the genetic and epigenetic factors associated with cocaine self-administration. Lastly, we will construct cell-type and circuit-specific gene regulatory networks that encapsulate the interplay of genetic and epigenetic factors. These networks will be established through rigorous computational analyses that integrate genomic, epigenomic, and transcriptomic data. In summary, this project aims not only to detail regulatory dynamics but also to identify key nodes and pathways for potential therapeutic intervention, representing a significant stride towards alleviating the global burden of cocaine use disorder. The work pushes the boundaries of current epigenetic studies in SUDs by employing a multidimensional approach to unravel the complex genetic and epigenetic landscapes governing cocaine response. The outcomes are expected to fundamentally enhance our understanding and present unprecedented avenues for therapeutic innovation.


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 = $492,000 )
2025	2025	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Drug Use and Addiction Research Programs	001	2	7/15/2025	NON-COMPETING CONTINUATION	$492,000
2025	2024	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Drug Use and Addiction Research Programs	000	1	7/15/2025	NEW	$0
														Subtotal = $492,000

Issue Date FY: 2024 ( Subtotal = $492,000 )
2024	2024	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Drug Use and Addiction Research Programs	000	1	7/31/2024	NEW	$492,000
														Subtotal = $492,000

Grand Total All Awards = $984,000

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The Genetic and Epigenetic Interplay of Cocaine Addiction: A Cell-Type, Circuitry, and Functional Dissection

Award Number: DP1DA061008

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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