# Integrating preclinical models to develop converging mechanistic data in co-occuring HIV and substance use

> **NIH NIH DP2** · DREXEL UNIVERSITY · 2022 · $222,260

## Abstract

Project Summary
Cocaine use disorders (CUDs) are highly comorbid with HIV infection and are characterized by a high propensity
to relapse even after protracted abstinence. With the success of antiretroviral therapies (ART), HIV-associated
mortality has substantially declined, resulting in a growing population of chronically HIV-infected, ART treated
adults in the United States. Both HIV infection and ART may interact with drug exposure to alter neurobiology,
thus creating a behaviorally and biologically distinct condition and requiring novel, targeted pharmacotherapeutic
strategies to reduce relapse to cocaine use. Relapse to drug use may be precipitated by drug craving. During
protracted withdrawal from repeated cocaine exposure, cocaine-seeking behavior becomes progressively
stronger, indicative of the “incubation of craving”. Development of strategies to reduce this craving have strong
potential to reduce relapse-related behaviors. Thus, research in this proposal is designed to complement the
parent award by investigating independent and combined effects of progressive HIV infection and daily ART
treatment on the neurobehavioral sequelae of the incubation of cocaine craving. The corticostriatal glutamate
system is a key regulator of relapse-related behavior. Disruption of glutamate homeostasis and
neuroinflammation occur with exposure to either cocaine or HIV infection. However, the impact of combined
protracted cocaine abstinence and HIV on neuroimmune function and glutamate system function is poorly
understood. This proposal will investigate the behavioral and neurobiological interactions between HIV and
incubated cocaine craving within key mesocorticolimbic structures that facilitate cocaine seeking (the medial
prefrontal cortex (mPFC) and nucleus accumbens (NAc)). We will test the overarching hypothesis that protracted
abstinence from cocaine interacts with HIV and ART to uniquely dysregulate glutamate homeostasis and
neuroimmune function, leading to potentiation of cocaine-seeking behavior. Aim 1 will determine the outcomes
of EcoHIV infection and daily ART treatment on cocaine craving in a cocaine conditioned place preference model
in male and female mice. Aim 2 will determine the effect of EcoHIV and daily ART on changes in glutamate
system markers and neuroimmune function in the mPFC and NAc. Findings from these studies will complement
the experiments outlined in the parent award and inform future research directions aimed at elucidating novel
pharmacotherapeutic targets for the treatment of substance use disorders in the context of progressive HIV and
ART. Further, the award of this administrative supplement will allow the candidate – an exceptionally well-
qualified Hispanic-Asian postdoctoral scholar - to gain hands-on training in models of comorbid progressive HIV
and cocaine exposure. Findings from the award are expected to serve as the basis for the development of an
independent line of research that will lead to subsequent fello...

## Key facts

- **NIH application ID:** 10615983
- **Project number:** 3DP2DA051907-01S1
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** JACQUELINE M BARKER
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $222,260
- **Award type:** 3
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10615983

## Citation

> US National Institutes of Health, RePORTER application 10615983, Integrating preclinical models to develop converging mechanistic data in co-occuring HIV and substance use (3DP2DA051907-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10615983. Licensed CC0.

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