# The impact of adolescent stress on neural circuits underlying punishment resistant reward seeking

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2024 · $44,187

## Abstract

PROJECT SUMMARY/ABSTRACT
Adolescence is a critical period of development characterized by rapid physiological and behavioral changes.
These widespread changes mark adolescence as a period of particular vulnerability to adverse experiences,
such as chronic stress. Indeed, chronic stress during adolescence is widely recognized as a risk factor for the
development of multiple psychiatric disorders, including addiction. With self-reporting of chronic stress on the
rise in adolescents—especially in the wake of the COVID-19 pandemic—there is an urgent need to understand
the effects of adolescent chronic stress on the neural mechanisms underlying behaviors linked to addiction.
Here, I examine one such behavior, punishment-resistant reward seeking, in which animals maintain their pursuit
of reward in the face of negative consequences.
This proposal aims to establish that a projection from the central amygdala (CeA) to the lateral substantia nigra
(SNL) is a key interface between stress and punishment-resistant reward-seeking. I hypothesize that chronic
stress in adolescence leads to enduring hyperexcitability of SNL-projecting CeA neurons, causing increased
inhibition of SNL GABA neurons and a net disinhibition of SNL dopamine neurons. I hypothesize that this
disinhibition of SNL dopamine neurons increases punishment-resistant reward seeking. I will test this hypothesis
using operant behavior, in vivo fiber photometry, and chemogenetics (Aim 1) alongside in vitro patch-clamp
electrophysiology (Aim 2). I will characterize long-term adaptations in the CeAàSNL pathway after adolescent
chronic stress along with the links between those neural adaptations and changes in the propensity for
punishment-resistant reward-seeking. My proposal will aid in the identification of the biological and behavioral
causes of addiction, in accordance with NIDA’s goals.
Over the course of this fellowship, I will receive training in teaching, communication, programming, and grant
writing. I will further my knowledge of drug abuse and addiction through coursework, practice, and conference
participation. Ultimately, this fellowship will support my goal of becoming an independent investigator studying
how perturbations in subcortical circuits during development lead to addiction and other psychiatric disorders.

## Key facts

- **NIH application ID:** 10899175
- **Project number:** 1F31DA060560-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Jacob Andrew Nadel
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $44,187
- **Award type:** 1
- **Project period:** 2024-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899175

## Citation

> US National Institutes of Health, RePORTER application 10899175, The impact of adolescent stress on neural circuits underlying punishment resistant reward seeking (1F31DA060560-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10899175. Licensed CC0.

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