# The role of corticotropin-releasing factor in modulating accumbal dopamine and producing escalation of drug intake

> **NIH NIH F31** · UNIVERSITY OF WASHINGTON · 2024 · $45,255

## Abstract

Project Summary/Abstract
Substances of abuse alter neural circuitry that result in the progression towards a substance use disorder
(SUD) in a subset of individuals. Currently, the United States is faced with an epidemic of SUD causing
immense human suffering and high overdose rates. Understanding the changes in neural circuitry that underlie
the transition to SUD-like behaviors, particularly in behaviors that have high risk such as escalated drug intake,
is key to designing and implementing new therapeutic techniques to combat this epidemic. The midbrain
dopaminergic system and particularly its projection to the Nucleus Accumbens (NAc) has been heavily
implicated in drug consumption and is believed to be involved in the addictive liability of drugs and the
progression to compulsive drug taking. Importantly, previous results from the Phillips lab demonstrated that
escalation of drug intake results from a decrement of the phasic dopamine signal to drug associated cues. The
driving force behind this degradation of phasic dopamine response related to drug consumption is unknown.
However, other neuromodulatory systems have also been implicated in drug consumption, such as
corticotropin releasing factor (CRF), and are capable of modulating the dopamine system. The overarching
hypothesis of this proposal is that CRF receptors in specific subpopulations of the NAc contributes to
escalation of drug intake through negatively modulating dopamine signaling. This hypothesis will be addressed
through two independent aims. Aim 1 will test the necessity of CRF receptor 1 in the NAc in the escalation of
drug taking via bilaterally knocking out CRF receptor 1 in NAc subpopulations using CRISPR/SaCas9
technology prior to a long access self-administration regime. Aim 2 will test the modulation of phasic dopamine
response via CRF receptor 1 in the NAc during escalation of drug taking via unilaterally knocking out CRF
receptor 1 and bilaterally measuring dopamine signaling in the NAc during long access self-administration via
fiber photometry coupled with a dopamine sensor. The results from this proposal will 1) outline the role of NAc
CRF receptors and 2) further investigate the contribution of dopamine modulation, both in the progression of
SUD-like phenotypes. Uncovering the neural mechanisms that drive SUD-like drug consumption will provide
therapeutic targets to combat SUD and related harms.

## Key facts

- **NIH application ID:** 10900194
- **Project number:** 1F31DA059249-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Lydia Gordon-Fennell
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $45,255
- **Award type:** 1
- **Project period:** 2024-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900194

## Citation

> US National Institutes of Health, RePORTER application 10900194, The role of corticotropin-releasing factor in modulating accumbal dopamine and producing escalation of drug intake (1F31DA059249-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10900194. Licensed CC0.

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