# Neuropeptide-dependent parabrachial control of the BNST during alcohol abstinence-induced negative affect

> **NIH NIH K99** · VANDERBILT UNIVERSITY · 2022 · $151,525

## Abstract

PROJECT SUMMARY/ABSTRACT
 Abstinence from alcohol use induces a negative affective state that can lead to maladaptive responses
to stress and relapse. Preclinical studies have begun to identify neurocircuits and peptide targets that regulate
negative affect during abstinence. As the field has begun to develop a deeper understanding of the circuitries
participating in addiction and negative affect, the next step is to understand how communication within these
circuits is modulated particularly at the neuropeptide and microcircuit level. The bed nucleus of the stria
terminalis (BNST) is a fundamental component of abstinence-relevant neurocircuitry as it modulates stress and
alcohol-related behavior in a neuropeptide-dependent manner. To investigate peptide-specific BNST circuitry
modulating negative-affect during abstinence, we will focus on afferents from the parabrachial nucleus (PBN),
a brainstem region that functions as a danger signal. PBN projections to the BNST release calcitonin gene-
related peptide (CGRP) and pituitary adenylate cyclase activating polypeptide (PACAP), peptides that
modulate pain and fear circuits, respectively. Our studies implicate heterogenous and sexually dimorphic
control within the PBNàBNST circuit as PBN projections induce heterogeneous ex vivo activity in BNST cells
and female-specific anxiety-like behavior with BNSTPBN activation. Furthermore, our preliminary studies
suggest a role for the PBN in alcohol-withdrawal, as inactivation is anxiolytic following alcohol exposure. This
proposal will significantly build on this foundational evidence by investigating how CGRP and PACAP
contribute to PBNàBNST circuit induced abstinence-induced behavior, in vivo and ex vivo activity.
Accordingly, the mentored K99 phase will build on my in vivo fiber photometry recordings and provide training
in ex vivo recordings to determine the role of CGRP on BNSTàPBN activity, abstinence-induced behavior
(AIM1), and the contribution of PACAP on the CGRP-neuromodulation (AIM2). The independent R00 phase
will investigate the role of PACAP on BNSTàPBN at the microcircuit level and alcohol-related states, with the
goal to further delineate the intricacies of peptide crosstalk (AIM3). The proposed studies and related career
development training plan in this MOSAIC Pathway to Independence Award collectively provide the ideal
mechanism to transition the applicant to a career as an independent addiction neuroscientist. The results will
significantly advance our understanding of neurocircuit mechanisms at the peptide and microcircuit level in
protracted abstinence while informing the use of peptidergic pharmacotherapies in alcohol use disorders.

## Key facts

- **NIH application ID:** 10463760
- **Project number:** 5K99AA029467-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Anel Ariana Jaramillo
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $151,525
- **Award type:** 5
- **Project period:** 2021-08-06 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463760

## Citation

> US National Institutes of Health, RePORTER application 10463760, Neuropeptide-dependent parabrachial control of the BNST during alcohol abstinence-induced negative affect (5K99AA029467-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10463760. Licensed CC0.

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