# Genetic pathways for impulsivity and drug reinforcement: DNA and transcriptome variation in mice

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $658,973

## Abstract

PROJECT DESCRIPTION
This project will chart with high-resolution the genetic pathways that give rise to defined clinical phenotypes
related to cocaine addiction. We will utilize the power of the hybrid mouse diversity panel (HMDP), combined
with high quality behavioral phenotyping and massive-scale RNA sequencing, to trace the interconnections
from DNA to RNA to clinical trait and provide layered information on the mechanisms of cocaine abuse. The
HMDP consists of 100 inbred and recombinant inbred strains and has a wide array of meiotic breakpoints. The
panel has been densely genotyped with more than 200,000 single nucleotide polymorphisms (SNPs), allowing
very fine mapping of quantitative trait loci (QTLs). Further, the HMDP is genetically stable and renewable and
can be assayed for multiple phenotypes, yielding cumulative biological information. We will expand our
previous HMDP-based studies of cocaine abuse-related traits by adding massive-scale RNA sequencing
(RNA-Seq), in order to detail the genetic control of the pathways to addiction. Our approach offers the distinct
advantage of mapping loci for known pathways as well as those involving variant and exotic RNA species. The
following aims are proposed: (1) We will quantitate intravenous self-administration of cocaine in HMDP mice.
This phenotype is regarded as being one of the most faithful models of cocaine abuse in animals and will allow
evaluation of QTLs that regulate addiction-related phenotypes. (2) We will perform RNA-Seq on two key areas
of the brain that play a role in the control of drug abuse, the medial prefrontal cortex (mPFC) and nucleus
accumbens (NAc) shell region. (3) We will analyze the combined datasets with powerful statistical tools to
understand the genetic regulation of drug abuse-related phenotypes. These studies will map genetic networks
and inter-tissue regulatory pathways for cocaine addiction and suggest new, highly specific therapeutic
strategies.

## Key facts

- **NIH application ID:** 9939498
- **Project number:** 5U01DA041602-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** ELEAZAR ESKIN
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $658,973
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939498

## Citation

> US National Institutes of Health, RePORTER application 9939498, Genetic pathways for impulsivity and drug reinforcement: DNA and transcriptome variation in mice (5U01DA041602-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9939498. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*