# Discovery of genetic and genomic mechanisms driving the relationship between social reward and cocaine addiction

> **NIH NIH R21** · MARSHALL UNIVERSITY · 2022 · $222,000

## Abstract

PROJECT ABSTRACT
Drug addiction is a critical public health crisis that is strongly genetically driven. A fundamental driver of human
addiction is the repeated choice to pursue a drug reward at the expense of a social reward, a strong reinforcer
of human behavior in non-addicted individuals. Despite the importance of this phenomenon in human
addiction, the genetic mechanisms underlying variation in the preference for a social reward over a drug
reward (henceforth social reward preference) have been totally unexplored because of the absence of a
relevant mouse model. Establishing a mouse model of social reward preference would enable leveraging the
vast mouse genetics toolkit for discovery and characterization of the mechanisms driving this trait, which, at its
extremes, represents vulnerability to and resistance to a key addiction vector. To this end, we propose to
harness the unprecedented genetic diversity of advanced mouse populations and the exceptional construct-
validity of the intravenous cocaine self-administration paradigm to discover genetic and genomic mechanisms
driving social reward preference. To quantify social reward preference in the mouse, we will use a recently
introduced paradigm for the rat in which the subject makes a binary choice to (1) intravenously self-administer
an addictive drug or (2) briefly interact with a conspecific. To capture maximum phenotypic variation and
enable discovery of genetic mechanisms driving social reward preference, we will use mice from the
Collaborative Cross (CC) mouse panel which contains 90% of the genetic diversity in the mouse species and
enables the integration of genomic and phenomic datasets across studies. In Aim 1 we will quantify the
preference for social reward relative to cocaine reward in male and female mice from eight CC strains. We will
quantify heritability of these phenotypes and identify strains exhibiting vulnerability and resistance to social
reward preference phenotypes (e.g., strong preference for a cocaine reward relative to a social reward, and
vice versa). In Aim 2 we will quantify gene expression in the nucleus accumbens following operant self-
administration of a social reward, yoked exposure to a social reward, and sham exposure to a social reward in
mice from the same eight CC strains used in Aim 1. We will perform RNA-seq in eight CC strains and scRNA-
seq in two extreme CC strains. We will integrate gene expression data (Aim 2) with behavioral data (Aim 1) to
identify cell-type specific gene expression signatures predictive of social reward preference. The successful
completion of these aims will provide (1) a foundation for future deep characterization of identified mechanisms
underlying social reward preference in mice; (2) a lasting community resource enabling genetic correlational
analysis among a subset of the CC strains across phenotypes, experiments, and laboratories; and (3) a refined
and robust pipeline for future characterization of social reward prefer...

## Key facts

- **NIH application ID:** 10520581
- **Project number:** 1R21DA054929-01A1
- **Recipient organization:** MARSHALL UNIVERSITY
- **Principal Investigator:** Price Evans Dickson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $222,000
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10520581

## Citation

> US National Institutes of Health, RePORTER application 10520581, Discovery of genetic and genomic mechanisms driving the relationship between social reward and cocaine addiction (1R21DA054929-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10520581. Licensed CC0.

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