# Role of PrRP+ projections to BNST in ethanol withdrawal and negative affective behavior

> **NIH NIH F32** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2024 · $77,284

## Abstract

Project Summary/Abstract
Negative affect and stress experienced during alcohol abstinence can be a major factor contributing to relapse
in alcohol use disorder, yet underlying neurobiological mechanisms remain ill-defined. Corticotropin-releasing
factor (CRF)-expressing neurons in the bed nuclei of the stria terminalis (BNST) are involved in anxiety and
stress responses, and they play a major role in the withdrawal. A subcommissural population of CRF neurons
in the BNST (vBNSTCRF) is heavily innervated by hindbrain noradrenergic neurons that co-express prolactin
releasing peptide (PrRP). Because these PrRP neurons are sensitive to both stress and interoceptive state,
they are likely involved in the development of stress hypersensitivity following withdrawal. However, the role of
PrRP neurons in alcohol-related behaviors has not been studied. I hypothesize that signaling of PrRP neurons
to vBNST during acute ethanol withdrawal contributes to the development of negative affective behaviors, and
that ethanol withdrawal potentiates vBNSTCRF responses to stress and PrRP neuronal activation. In the
proposed project, mice will undergo chemogenetic silencing of PrRP+ neurons projecting to vBNST during
acute ethanol withdrawal to examine the necessity of the circuit in the development of negative affective
behaviors (Aim 1). Then, the influence of ethanol withdrawal on in vivo calcium responses of vBNSTCRF
neurons to stress and chemogenetic activation of PrRP+ neurons will be explored using fiber photometry (Aim
2). Finally, monosynaptic tracing and whole brain imaging will be used to define additional brain regions
innervating vBNSTCRF neurons that may be modulated concomitantly during ethanol withdrawal (Aim 3). The
results of these studies will provide an improved understanding of neurobiological mechanisms impacting
affective behavioral changes during ethanol abstinence. This project also provides a strong platform to expand
and strengthen the trainee’s expertise in modern behavioral neuroscience approaches, including intersectional
viral strategies for chemogenetic manipulation of neural circuits, observation of cell-type specific in vivo
calcium signaling, and characterization of monosynaptic inputs to specific cell populations.

## Key facts

- **NIH application ID:** 10899924
- **Project number:** 1F32AA031404-01A1
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Caitlyn Marie Edwards
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $77,284
- **Award type:** 1
- **Project period:** 2024-07-01 → 2025-10-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899924

## Citation

> US National Institutes of Health, RePORTER application 10899924, Role of PrRP+ projections to BNST in ethanol withdrawal and negative affective behavior (1F32AA031404-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10899924. Licensed CC0.

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