Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Genetic substrates of cue-reactivity and cocaine motivation

Award Number: U01DA060669
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2025
PERIOD OF PERFORMANCE END DATE: 04/30/2030

Group Awards By:

View Award Description

Genetic substrates of cue-reactivity and cocaine motivation - PROJECT SUMMARY Understanding the genetic factors that contribute to the transition from recreational to problematic drug use is vital for uncovering biological mechanisms that can aid in preventing and treating substance use disorders (SUDs). Genome wide association studies (GWAS) have been successful in identifying genetic variants, but validating these genes is diĜcult given that human research is limited to non-invasive approaches. Other approaches include integrating GWAS results with large-scale ‘omics’ datasets, and conducting functional studies in animal models. One such model is the intermittent-access cocaine self-administration procedure (IntA), which triggers increased cocaine motivation (i.e., incentive sensitization) in rats after only limited amounts of drug exposure. This models the transition into early stages of SUD and, when compared to other procedures, can be used to dissociate total drug intake from incentive sensitization. To uncover the genetic factors behind incentive sensitization during IntA, our team has conducted a GWAS in a limited sample of heterogeneous stock rats and identiffied genomic regions that inĚuence cocaine motivation and contain several candidate genes. Increasing the power of this study in Aim 1 will enable the discovery of additional gene variants contributing to the complex genetic landscape of SUD. Yet, candidate genes must be investigated with follow-up studies. In a separate project, multi-level ‘omics’ data (including GWAS results, phenome-wide association studies, and transcriptomics) were integrated to identify candidate gene variants underlying cue-reactivity, a trait that that is phenotypically and genetically correlated with measures of cocaine-cue reactivity. These candidates included the understudied genes Tenm4 and Far1. Subsequent behavioral neuroscience-based approaches established that administration of a Tenm4-associated peptide reduced several measures of cocaine motivation during IntA and thus conffirmed Tenm4's pleiotropic eěect on cocaine motivation and cue-reactivity. However, further characterization of Tenm4 and Far1 is needed, thus another goal of this project is to use CRISPR-based transcriptional manipulation to determine the roles of these genes in cocaine cue-reactivity and motivation (Aim 2). Finally, another approach for validating GWAS ffindings involves generating polygenic scores (PGSs) that can be used to predict cue-reactivity in naïve rats. In Aim 3, these PGSs will be used to determine the interaction between genetic vulnerability to cue-reactivity and changes in drug motivation during multiple cocaine self-administration paradigms. Thus, this project will enhance the understanding of genetic factors inĚuencing SUD susceptibility, validate candidate genes, and determine how genetic predisposition interacts with drug exposure to produce addiction- like behaviors. These goals align directly with those of those of the NIDA Animal Genomics Program, that is, “to identify [genetic variants] that underlie … phenotypes associated with addictive behaviors … behaviors associated with SUD, [and] uncover the function of known or newly discovered genetic or epigenetic variants”.


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 = $798,919 )
2026	2026	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	002	2	7/6/2026	NON-COMPETING CONTINUATION	$12,699
2026	2026	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	000	2	5/8/2026	NON-COMPETING CONTINUATION	$774,422
2026	2025	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	001	1	7/3/2026	NEW	$11,798
														Subtotal = $798,919

Issue Date FY: 2025 ( Subtotal = $790,937 )
2025	2025	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	000	1	7/28/2025	NEW	$790,937
														Subtotal = $790,937

Grand Total All Awards = $1,589,856

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Genetic substrates of cue-reactivity and cocaine motivation

Award Number: U01DA060669

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 08/01/2025

PERIOD OF PERFORMANCE END DATE: 04/30/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer