# Genetic substrates of cue-reactivity and cocaine motivation

> **NIH DA U01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2026 · $774,422

## Abstract

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 conffirme

## Key facts

- **NIH application ID:** 11379941
- **Project number:** 5U01DA060669-02
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Paul J Meyer
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** DA
- **Fiscal year:** 2026
- **Award amount:** $774,422
- **Award type:** 5
- **Project period:** 2025-08-01T00:00:00 → 2030-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11379941

## Citation

> US National Institutes of Health, RePORTER application 11379941, Genetic substrates of cue-reactivity and cocaine motivation (5U01DA060669-02). Retrieved via AI Analytics 2026-05-20 from https://api.ai-analytics.org/grant/nih/11379941. Licensed CC0.

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