# Genetics of Amphetamine Preference

> **NIH NIH R21** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $191,521

## Abstract

––– PROJECT SUMMARY/ABSTRACT ––––––––––––––––– R21/R33: Genetics of Amphetamine Preference. ––––
Substance used disorder (SUD) is still highly prevalent in the US, and the recent pandemic has made its
prevalence increase even more. Genetic factors account for a substantial driving force for the development of
SUD, and in recent years ~50 human genes have been associated with psychostimulant use in numerous
genetic studies. Many of these genes have not previously been studied for their role in SUD, neither in human
samples, nor in model organisms. Thus, their causative role in driving the development of SUD has yet to be
elucidated. Furthermore, some associations have highlighted single nucleotide polymorphisms between two
human genes, rendering the question of causality even harder to determine. This gap has also been
highlighted by funding agencies, and it has led NIDA to issue a Program Announcement for the “Functional
Validation and/or Characterization of Genes or Variants Implicated in Substance Use Disorders” (NIDA PAR-
23-041). The vinegar fly, Drosophila melanogaster, has been a genetic model organism for more than a
hundred years. Major strides have been made in the last 15 years studying the behavioral responses to
alcohol and other drugs of abuse in flies. This applies regarding the characterization of novel genes and
pathways that are also conserved in humans, and it applies for the development of new assays that resemble
endophenotypes of addiction more closely as well. Based on our recent development of a robust experience-
dependent amphetamine preference (EDAP) assay with high throughput, we here propose to test 20 human
candidate SUD genes for their in vivo role in the development of amphetamine preference (Aim1/R21 phase).
In order to progress to the R33 phase of the proposal, we will validate ≥1 human candidate SUD gene for an
amphetamine preference phenotype in concordant, independent replication experiments that use two distinct
tools of genetic manipulation, for example, one short-guide RNA for CRISPR/Cas9-mediated knock out
generation and one RNA-interference line to cause gene knock down. In the following R33 phase we propose
to functionally characterize 1-3 candidate SUD genes. We will test predicted interaction partners for their role
in amphetamine preference, identify the conserved neurotransmitter systems that require these genes for wild-
type amphetamine preference, and will determine effects on RNA levels and on genome accessibility.
Together, these data will both validate genes implicated in SUD and lead to the “identification of new targets
for future addiction therapeutics” (NIDA PAR-23-041).

## Key facts

- **NIH application ID:** 10894480
- **Project number:** 1R21DA060453-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Adrian Rothenfluh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $191,521
- **Award type:** 1
- **Project period:** 2024-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894480

## Citation

> US National Institutes of Health, RePORTER application 10894480, Genetics of Amphetamine Preference (1R21DA060453-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894480. Licensed CC0.

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