# HIV effects on astrocytic regulation of stress-induced cocaine reinstatement

> **NIH NIH R03** · DREXEL UNIVERSITY · 2024 · $151,500

## Abstract

PROJECT SUMMARY
HIV infection is commonly co-occurring with drug use. Both HIV infection and drug use are associated with
adrenal dysfunction and hormonal dysregulation, which can drive impairments in response to stress. Stress is a
major factor affecting HIV disease outcomes and susceptibility to relapse, however there is a lack of
understanding of the factors that promote relapse in people living with HIV. Responsivity to stress is regulated
by the glucocorticoid, cortisol. HIV can result in enhanced basal cortisol levels, but reduced cortisol responses
to stress. In contrast, cocaine dependence is associated with enhanced basal and stress-induced cortisol
responses. However, the interaction of HIV infection and cocaine use on cortisol levels is not well characterized.
In rodent models, cocaine exposure enhances the corticosterone response to stress in male and female rodents,
while tat transgenic male, but not female, mice exhibit blunted corticosterone responses to stress. Thus, HIV-
infected females may be more vulnerable to stress-induced reinstatement of cocaine seeking due to lack of
blunted corticosterone responses by tat. Glucocorticoid signaling at astrocytes may be an important mediator of
this response. The glucocorticoid receptor can be downregulated in response to stress, and this effect appears
to be specific to astrocytes. Astrocytes are also important mediators of relapse-related behaviors and are
independently regulated by cocaine and HIV infection. Further, modulation of glucocorticoid receptors regulates
astrocytic calcium signaling, suggesting that stress modulates astrocytic activity. Our preliminary data indicate
that stress-induced reinstatement of reward seeking is associated with enhanced astrocytic calcium signaling in
the reward-paired context. Thus, astrocytic glucocorticoid signaling may be a potential regulator of the stress
response and stress-induced relapse-like behavior in the context of HIV infection. Aim 1 will determine the effects
of EcoHIV inoculation on stress-induced corticosterone levels and astrocytic glucocorticoid receptor expression
following a history of cocaine exposure in male and female mice. Male and female mice will be inoculated with
EcoHIV and undergo cocaine exposure and withdrawal, and then be subjected to forced swim stress. Serum
corticosterone levels and immunofluorescent labeling of astrocytic GR will be assessed to determine if female
mice exhibit enhanced stress responses following EcoHIV infection. Aim 2 will determine whether EcoHIV
infection sex-specifically promotes stress-induced reinstatement of cocaine seeking. Male and female mice will
be inoculated with EcoHIV and be trained in a conditioned place preference paradigm for cocaine, followed by
extinction and reinstatement following forced swim stress exposure to determine if EcoHIV-infected female mice
exhibit enhanced stress-induced reinstatement. The results of these experiments will identify a potential target
for reducing ...

## Key facts

- **NIH application ID:** 11009252
- **Project number:** 1R03DA060771-01A1
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Laura L Giacometti
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $151,500
- **Award type:** 1
- **Project period:** 2024-06-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11009252

## Citation

> US National Institutes of Health, RePORTER application 11009252, HIV effects on astrocytic regulation of stress-induced cocaine reinstatement (1R03DA060771-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11009252. Licensed CC0.

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