# Functional mapping of arginine vasopressin receptor 1A circuits that promote anorexic behavior

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $462,109

## Abstract

PROJECT SUMMARY
Anorexia nervosa (AN) has the highest mortality rate of any psychiatric disease, and there are no
effective treatments. A major obstacle to identifying new therapeutic targets is the lack of insight
into causes of the pathophysiological eating behavior. Malnutrition and co-morbid psychiatric
illnesses cause dramatic changes in the brain and periphery that complicate efforts to uncover
factors responsible for disease onset. The Zeltser lab developed a new mouse model to study AN
at the stage of illness prior to disease conversion by taking advantage of an epidemiological
observation that is often overlooked – genetic susceptibility in adolescence. Female mice carrying
an allele associated with genetic susceptibility to AN (BDNF-Val66Met) were exposed to social
isolation stress and caloric restriction during adolescence. Approximately 40% of these mice
exhibit severe self-imposed dietary restriction, sometimes to the point of death. Studies using this
mouse model of the pre-AN state identified a novel therapeutic target for AN treatment: arginine
vasopressin receptor 1A (AVPR1A).
The proposed experiments will map the AVP→ AVPR1A circuits in the brain that are necessary
and sufficient to suppress feeding and will determine which are potentiated by gene x environment
interactions that promote susceptibility to anorexic behavior. Studies outlined in Aim 1 will utilize
pharmacological, genetic and pharmacogenetic approaches to define populations of AVPR1A
neurons that are necessary and sufficient to suppress feeding in wild-type mice. In parallel,
experiments in Aim 2 will use a combination of retrograde tracing and pharmacogenetic
techniques to identify neuronal populations that transmit the anorexic AVP signal. Since there are
many distinct circuits that regulate feeding, studies in Aim 3 will determine where anorexic effects
of AVP and the expression of AVPR1A pathway components are enhanced in hBDNFMet/? females
exposed to peri-pubertal social isolation stress.
The elucidation of brain circuits that promote anorexic behavior in our mouse model would provide
a strong foundation for future efforts to explore whether AVPR1A antagonists that are currently in
Phase II clinical trials for other psychiatric indications could benefit some AN patients. Lessons
learned will also significantly advance the understanding of how the common BDNF-Val66Met
variant exacerbates the effects of social stress on the adolescent brain to increase susceptibility
to a variety of anxiety-related and affective disorders.

## Key facts

- **NIH application ID:** 10073542
- **Project number:** 5R01MH113353-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Lori M Zeltser
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $462,109
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073542

## Citation

> US National Institutes of Health, RePORTER application 10073542, Functional mapping of arginine vasopressin receptor 1A circuits that promote anorexic behavior (5R01MH113353-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10073542. Licensed CC0.

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