# Psychological stress susceptibility in juvenile female and male mice

> **NIH NIH R16** · UNIVERSITY OF TEXAS EL PASO · 2022 · $153,375

## Abstract

Program Director/Principal Investigator (Iñiguez, Sergio, Diaz):
ABSTRACT
 Epidemiologic reports indicate that mood-related illnesses, like major depressive disorder (MDD), are
among the leading cause of morbidity and mortality in the juvenile population. To make matters worse, women
are twice as likely to be diagnosed with MDD, a sex difference that becomes apparent during the adolescent
stage of development. These disparities highlight the critical need for the development of novel preclinical
models to uncover the neurobiological factors that underlie MDD as a function of age and sex – particularly,
because most animal models mainly incorporate adult male rodents. To address this issue, our group
developed the vicarious defeat stress (VDS) paradigm wherein a mouse witnesses the defeat bout of a male
conspecific from the safety of an adjacent compartment, leading to a behavioral outcome that resembles some
of the core symptoms of MDD (deficits in sociability, decreased preference for reward-related stimuli and body
weight, along with increased helplessness behavior and corticosterone). A major strength of this innovative
approach is that it allows for the experimental inclusion of females and juveniles – vulnerable populations that
are commonly excluded in preclinical/clinical studies. As such, the experiments described in this proposal will
evaluate whether exposing juvenile female and male mice to VDS results in behavioral outcomes that
recapitulate a depression-related phenotype. This will be accomplished within the framework of the following
specific aims: [1] assess the behavioral consequences of VDS on sensitivity to reward (cocaine, sucrose),
affect, and memory-performance in adolescent female and male mice (postnatal day 35). Also, [2] to evaluate
if traditional (fluoxetine) and novel (ketamine) antidepressant medications can reverse the VDS-induced
behavioral deficits observed. Lastly, [3] to evaluate the integrity of mood-related biological markers [brain
derived neurotropic factor (BDNF)-related signaling] within the hippocampus. It is expected that juvenile VDS
will mediate behavioral alterations associated with enhanced drug abuse potential (i.e., cocaine), anhedonia
(decreased sucrose preference), maladaptive responses to subsequent inescapable stress (despair), and
memory-related impairment. Furthermore, that clinically relevant medications (fluoxetine and ketamine) will
reverse the VDS-induced social dysfunction, mimicking what is observed at the clinic in juvenile populations.
Additionally, it is expected that site-specific neurochemical adaptations (BDNF fluctuations within the
hippocampus) will be observed after VDS exposure in an age and sex specific manner. Collectively, the
outcome of these studies will provide behavioral, pharmacological, and molecular evidence of VDS-induced
dysfunction that may underlie the convergent (both sexes experiencing MDD) and divergent (age- and sex-
specific) neurobiological underpinnings of M...

## Key facts

- **NIH application ID:** 10412410
- **Project number:** 1R16GM145552-01
- **Recipient organization:** UNIVERSITY OF TEXAS EL PASO
- **Principal Investigator:** Sergio Diaz Iniguez
- **Activity code:** R16 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $153,375
- **Award type:** 1
- **Project period:** 2022-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412410

## Citation

> US National Institutes of Health, RePORTER application 10412410, Psychological stress susceptibility in juvenile female and male mice (1R16GM145552-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10412410. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*