# Surprising roles of corticotropin releasing factor (CRF) neurons in reward motivation

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $37,229

## Abstract

PROJECT SUMMARY. The primary goal of this proposal is to investigate the motivational role of excitation of
neurons that release corticotropin releasing factor (CRF) in brain limbic structures. CRF neural circuitry is the
brain's master stress trigger1. The activation of CRF neurons is traditionally believed to generate aversive
motivational states including aversive withdrawal states after discontinuation of drug use in addicts1,2,3.
Specifically, excitation of CRF neurons in both the central amygdala (CeA) and in the bed nucleus of the stria
terminalis (BNST) are hypothesized to generate aversive withdrawal states1,2,4 according to opponent-process
models (also called hedonic homeostasis, hedonic dysregulation and allostasis hypotheses of addiction).
However, other research, including my own pilot studies, demonstrates that activation of CRF neurons in CeA,
as well as NAc, may also contribute to intensifying positive incentive motivation for rewards, without inducing
any aversive states5,6,7. If so, this would help explain why stress continues to precipitate relapse in recovering
addicts even after withdrawal symptoms are gone. My pilot evidence suggests that only CRF neurons in BNST
cause a traditional aversive state when activated. The current proposal aims to investigate the surprising
positive incentive motivation roles of CRF neurons in CeA and NAc, using selective optogenetic tools to
specifically activate CRF-expressing neurons in CRH-Cre rats, via Cre-targeted optogenetic channelrhodopsin.
The predicted positive incentive motivation effects of CRF-neuron stimulation in NAc and CeA will be
contrasted to predicted negative aversive effects of CRF-neuron stimulation in BNST. Motivation effects
of inhibiting CRF neurons will also be examined in these structures. Incentive motivation amplification will be
measured using laser self-stimulation of CRF neurons and an operant 2-choice task earning sensory rewards,
which models narrowly focused intense pursuit, similar to addiction8,9. In this choice task, rats earn either sucrose
rewards or intravenous drug rewards: one of the two reward choices always earn a reward accompanied by laser
that modulates CRF neuronal activity, while the other choice earns the reward alone. Finally, distributed neural
circuitry recruited by stimulation of CRF neurons that mediate incentive motivation for CeA or NAc sites, or
aversive motivation for BNST sites, will be mapped and compared by measuring distant Fos expression in other
brain structures, and specific causal projections will be examined using optogenetic tools. Through the proposed
training, I will learn new techniques including intravenous drug self-administration procedures and behavioral
economics analysis, and advanced optogenetic and immunohistochemistry techniques needed for CRF neuron
imaging and tract tracing, and for mapping anatomical activation patterns. This training will help me to develop
into a productive, independent research scientist. Th...

## Key facts

- **NIH application ID:** 9912629
- **Project number:** 5F31DA047738-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Hannah Marian Baumgartner
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,229
- **Award type:** 5
- **Project period:** 2019-05-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912629

## Citation

> US National Institutes of Health, RePORTER application 9912629, Surprising roles of corticotropin releasing factor (CRF) neurons in reward motivation (5F31DA047738-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9912629. Licensed CC0.

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