# Mechanisms underlying prescription opioid use post social defeat in HIV+ adolescents

> **NIH NIH R21** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2024 · $195,971

## Abstract

Abstract
From a developmental milestone, adolescence is a very critical phase since there are a plethora of changes
occurring on different tiers - physical, cognitive, emotional, social, and behavioral. Any negative experiences at
this critical developmental period can significantly impact the outcomes with serious ramifications that could
persist into adulthood. This problem is further aggravated in HIV+ adolescents due to the associated stigma,
negative attitudes, and prejudice in society. Social defeat (SD) employing a resident-intruder paradigm mimics
bullying in humans and is considered a relevant animal model of psychosocial stress in defeated individuals.
While previous literature has reported the experience of social stress to correlate with a higher incidence of
stress-related psychiatric and addictive disorders, molecular mechanisms contributing to these outcomes still
remain unclear. Our goal is on discerning molecular mechanisms and focuses on decoding the role of
extracellular vesicles (EV) in exacerbating synaptic function and precipitating prescription opioid use in HIV+
adolescents post SD. Our preliminary studies using a preclinical model: HIV transgenic rats have revealed
alterations in brain derived EV (BDEV) sizes with HIV infection. Based on this premise, our overarching central
hypothesis is SD in HIV+ adolescent rats further exacerbate BDEV dynamics that aggravate synaptic injury and
precipitates prescription opioid use. Under Aim 1, we seek to elucidate if SD in HIV+ adolescent rats dysregulate
dynamics of BDEV biogenesis and increases vulnerability to prescription opioid use. In Aim 2 we will delineate
mechanisms associated with adolescent HIV+ BDEVs post SD elicit higher inflammation and exacerbate
synaptic injury. Upon completion of these goals, we expect to significantly enhance our knowledge of the role of
BDEVs to regulate brain function post SD in HIV+ adolescents and identification of novel BDEV protein markers.
Such information gleaned will further fuel mechanistic studies and eventually help develop future strategies to
treat and improve neurological outcomes in this vulnerable population.

## Key facts

- **NIH application ID:** 10832058
- **Project number:** 5R21DA058588-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Gurudutt Pendyala
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $195,971
- **Award type:** 5
- **Project period:** 2023-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832058

## Citation

> US National Institutes of Health, RePORTER application 10832058, Mechanisms underlying prescription opioid use post social defeat in HIV+ adolescents (5R21DA058588-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10832058. Licensed CC0.

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