# The Integrated Role of Vasopressin and Oxytocin Receptors in the Modulation of BNST Activity and Fear Processing

> **NIH NIH R01** · ROSALIND FRANKLIN UNIV OF MEDICINE & SCI · 2022 · $491,427

## Abstract

SUMMARY: Anxiety disorders are the most common psychiatric conditions, yet no new anxiolytic drug has
been approved for treatment in the last decade. Therefore, there is a significant unmet need to develop new
effective pharmacotherapies. In rodent and human studies, the bed nucleus of the stria terminalis (BNST) has
emerged as a key brain region translating prolonged exposure to uncertain threats into sustained fear. The
BNST is hyperactive in patients suffering from anxiety disorders and post-traumatic stress disorder. Human
imaging studies demonstrate an enhanced functional connectivity between the BNST and the central amygdala
(CeA) in anxious individuals. In rats, the BNST sends inhibitory projection to the CeA (BNSTàCeA) but there
is a significant knowledge gap on how the BNST interacts with the CeA to modulate fear processing. As the
CeA and BNST drive fear responses to predictable and unpredictable threats, respectively, increased activity
of the BNSTàCeA neurons will favor responses to the unpredictable threats and can precipitate
hypervigilance, an important hallmark of anxiety disorders in humans. Therefore, the factors that inhibit this
BNSTàCeA output have untapped potential as novel therapeutic targets. Recent findings from the lab show
that one such target involves oxytocin receptors (OTR) in the BNST, as OTR activation inhibits BNSTàCeA
output and facilitates fear to predictable threats (cued fear). In contrast, our compelling preliminary data
indicate that activation of vasopressin 1a receptor (V1aR) in the BNST directly excites Type III/Corticotropin-
releasing factor (CRF) neurons, which promote sustained fear responses. Based on this scientific premise, the
central hypothesis of this proposal is that by inhibiting and exciting the BNSTàCeA neurons, OTR and V1aR
facilitate fear responses to predictable vs. unpredictable threats, respectively. This innovative concept will be
investigated using cutting-edge experimental approaches, including chemogenetic and optogenetic
manipulations of BNSTàCeA neurons in recently developed transgenic rat models (OTR-Cre, AVP-Cre, CRF-
Cre). Rigorously designed behavioral and electrophysiological experiments will test the hypothesis with the
following specific aims: 1) Determine the integrated role of V1aR and OTR in modulating activity of BNST
neurons, 2) Determine whether predictable vs. unpredictable threats differentially modulate activity of
BNSTàCeA neurons via OTR and V1aR, 3) Determine the role of BNSTàCeA neurons in mediating fear
responses to predictable vs. unpredictable threats, and the contribution of OTR vs. V1aR. By refining
mechanisms underlying the activity of BNSTàCeA neurons, this proposal will have a positive impact on the
understanding how an imbalance in processing of predictable vs. unpredictable threats can lead to a
hypervigilance and precipitate the onset of anxiety disorders.

## Key facts

- **NIH application ID:** 10530987
- **Project number:** 2R01MH113007-06A1
- **Recipient organization:** ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
- **Principal Investigator:** Joanna Dabrowska
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $491,427
- **Award type:** 2
- **Project period:** 2017-05-12 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10530987

## Citation

> US National Institutes of Health, RePORTER application 10530987, The Integrated Role of Vasopressin and Oxytocin Receptors in the Modulation of BNST Activity and Fear Processing (2R01MH113007-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10530987. Licensed CC0.

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