# Determining the effect of early resource scarcity on adolescent addiction-related behavior and cell-type specific transcription

> **NIH NIH R21** · GEORGIA STATE UNIVERSITY · 2023 · $267,380

## Abstract

PROJECT SUMMARY
Early life experiences can have long-lasting consequences on risk and resilience for developing substance use
disorder (SUD). While trauma early in life increases risk for SUD, brief early stressor exposure can promote
stress inoculation or later resilience. Much of the preclinical work studying how the early environment affects
addiction-related behaviors has focused on outcomes in adult animals. However, this approach misses how early
experiences alter the trajectory of the development of brain regions implicated in SUD and limits our ability to
know if interventions for SUD would be effective earlier, such as in adolescence, when first exposure to drugs of
abuse often occurs. This proposal addresses this gap and tests how a rat model of brief early resource scarcity
alters adolescent impulsivity, opioid taking, and cell-type specific transcription in the medial prefrontal cortex
(mPFC), a key part of the reward circuitry that is developing in adolescence. This proposal builds on our labs
extensive work characterizing the effects of the limited bedding/nesting (LBN) manipulation on adult addiction-
related outcomes. In LBN, dams and pups are in a low resource environment during pups first week of life and
effects are compared to rats raised with adequate resources throughout development. We previously found that
LBN causes sex-specific resilience to addiction-related behaviors, reducing impulsive choice and morphine
taking, in adult male but not in adult female rats. We also found alterations in glutamatergic signaling in reward
circuitry in adult LBN males that can contribute to resilience. This proposal will extend this work to determine, for
the first time, whether LBN causes similar behavioral and molecular changes in adolescent rats. Aim 1 will used
innovative new behavioral procedures that allow for testing impulsive choice with delayed discounting and
morphine self-administration in adolescent rats. We expect that, like in adulthood, LBN will promote male-specific
resilience to adolescent impulsivity and drug taking. Aim 2 will build on new unpublished single nucleus RNA
sequencing (scRNAseq) assessing how LBN alters cell-type specific transcription in the adult mPFC. This
approach overcomes limitations of past work using bulk tissue where transcriptomic alterations cannot be
assigned to any particular cell type. In adults, we found that LBN alters genes in one subtype of excitatory
glutamatergic neurons in the mPFC of only adult males and several of these genes are involved in vesicular
transport, which could lead to altered presynaptic glutamate release. Here we will test the prediction that LBN
causes similar male-specific transcriptional alterations in glutamatergic neurons in adolescents, while also
discovering novel gene expression changes within genetically defined subtypes of cells in the mPFC. By
combining this novel adolescent phenotyping with prior adult work, we can determine how LBN affects the
developmental ...

## Key facts

- **NIH application ID:** 10825012
- **Project number:** 1R21DA059966-01
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** Debra A Bangasser
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $267,380
- **Award type:** 1
- **Project period:** 2023-09-30 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825012

## Citation

> US National Institutes of Health, RePORTER application 10825012, Determining the effect of early resource scarcity on adolescent addiction-related behavior and cell-type specific transcription (1R21DA059966-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10825012. Licensed CC0.

---

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