# Identification of genetic features of delay discounting using a heterogeneous stock rat model

> **NIH NIH U01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $465,160

## Abstract

PROJECT SUMMARY
This application is responsive to PAR-15-120 (Identification of Genetic and Genomic Variants by Next-Gen
Sequencing in Non-Human Animal Models).
Substance use disorders are often characterized by heightened preference for small, immediate over larger,
delayed rewards (“delay discounting”). Research has successfully related this type of impulsive decision-
making bias with etiological factors predictive of drug use, with the progression to regular use, and with the
likelihood of succeeding in cessation efforts. Research has also begun to identify the neural and genetic
correlates of delay discounting. However, research identifying the specific genes associated with this
phenotype remains ambiguous. Accordingly, the primary objective of the proposed work is to increase our
understanding of the genetic basis of delay discounting, thereby providing a better understanding of
impulsivity. Four aims are proposed to accomplish this objective. Aim 1 will phenotype 600 heterogeneous
stock (HS) rats for delay discounting using the adjusting amount procedure (Richards et al. 1997; Wilhelm and
Mitchell 2009) so that Genotyping-By-Sequencing (GBS) can detect behavioral quantitative trait loci (bQTLs).
Aim 2 will use bi-directional short-term selective breeding on a subset of these HS rats to form high (HD) and
low (LD) delay discounting selected lines based on relative preference for the small, immediate reward over
the larger later reward. Rats from the 4th generation of selection will be used to identify changes in allele
frequency due to selection by genotyping the LD and HD selected lines using GBS and gene dropping. Aim 3
will sequence the brain transcriptome in 200 phenotyped HS rats to characterize the gene expression
signatures for delay discounting in three brain regions of interest: nucleus accumbens core, the prelimbic
cortex and the basolateral amygdala. The sufficiency of these signatures to predict selection targets will be
evaluated by analyzing the transcriptomes (RNA-Seq) from HD and LD selected lines at the 4th generation of
selection collected under Aim 2. Aim 4 will examine HD and LD rats' performance on other measures of
impulsivity, including performance on a within sessions measure of delay discounting, the stop signal task and
the 5-choice serial reaction time task. This will permit us to examine genetic correlates of delay discounting,
and lay a foundation for research examining the shared genetic bases of these other behavioral phenotypes of
impulsivity.
Identifying the genotype and functional genetics for expression of high or low levels of delay discounting will
facilitate identification of individuals at risk for developing substance use disorders and other
psychopathologies. It will provide information about the transcriptomics of impulsive choice, and encourage
future explorations of the neurogenetics of this type of decision-making bias.

## Key facts

- **NIH application ID:** 10146324
- **Project number:** 5U01DA046077-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** ROBERT J. HITZEMANN
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $465,160
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146324

## Citation

> US National Institutes of Health, RePORTER application 10146324, Identification of genetic features of delay discounting using a heterogeneous stock rat model (5U01DA046077-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10146324. Licensed CC0.

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