# Gene Regulation in Memory Circuits as a Consequence of Polysubstance Use

> **NIH NIH R01** · BROWN UNIVERSITY · 2024 · $500,864

## Abstract

PROJECT SUMMARY:
Methamphetamine is a highly addictive drug that has major effects on the brain’s learning and memory
systems. Methamphetamine use is commonly predicted by high use of legal psychostimulants such nicotine or
alcohol, but the mechanisms underlying sequential use of alcohol, nicotine and methamphetamine are not well
understood. Both nicotine and alcohol alter the function of brain circuits required for adaptive decisions, but the
cellular and molecular mechanisms through which this occurs largely remain a mystery. Identifying the gene
regulatory networks within select circuits in high alcohol or high nicotine seeking animals and deciphering how
methamphetamine alters these networks is necessary to decode the fundamental molecular underpinnings
through which methamphetamine influences maladaptive choice. However, the diversity of circuits and cells
involved in these responses has confounded our ability to identify key molecular pathways. Our goal is to use a
genes-circuits-behavior approach in Drosophila melanogaster to provide an innovative and holistic
understanding of the core fundamental principles through which sequential use of psychostimulants alter the
molecular landscape and neural dynamics of memory circuits to alter behavioral decisions. Transcriptional
regulation within memory circuits is a fundamental process through which psychostimulants drive maladaptive
changes in the brain function. This work provides the causal gene regulatory mechanisms through which high
preference for alcohol or nicotine affects methamphetamine response in memory circuits. This has major
implications for how co-use of psychostimulants alters the molecular landscape that drives drug-seeking
behavior.

## Key facts

- **NIH application ID:** 10896244
- **Project number:** 5R01DA058947-02
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Karla R. Kaun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $500,864
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896244

## Citation

> US National Institutes of Health, RePORTER application 10896244, Gene Regulation in Memory Circuits as a Consequence of Polysubstance Use (5R01DA058947-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10896244. Licensed CC0.

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