# Cocaine Abuse and HIV Comorbidity: Relapse-Related Brain Pathology.

> **NIH NIH R21** · RUSH UNIVERSITY MEDICAL CENTER · 2020 · $196,250

## Abstract

SUMMARY
Cocaine abuse is prevalent in HIV-infected individuals. Drug abstinence greatly improves the health and well-being of the
comorbid individual, but relapse to drug-taking remains exceptionally high in this vulnerable population. In the brain, the
actions of HIV-associated proteins and cocaine may overlap on glutamatergic pathways and the innate immune system.
Glutamate transmission clearly regulates relapse and a role for inflammation in addiction is becoming appreciated. Thus,
relapse-related neuropathology in the comorbid condition is likely to be vastly different from that described for cocaine
abuse alone. The overarching objective of this research program is to decipher neurobiological mechanisms that underpin
abstinence and relapse to cocaine-taking during HIV-infection. This objective requires valid animal models of the human
comorbid condition. Intravenous (i.v.) self-administration protocols are the ‘gold standard’ facsimile of human drug-
taking. To our knowledge, we are one of only two laboratories world-wide that have implemented these protocols for
cocaine in a rodent model of human HIV/AIDS, and there are no studies using a comorbid model to study relapse to
cocaine-taking. Thus, the interactions between HIV infection and cocaine use on the neurobiological underpinnings of
relapse are completely unexplored. Moreover, i.v. does not emulate the routes of cocaine administration used by humans.
To fill these gaps, the objectives of this R21 project are to implement a new, clinically relevant model of the human
comorbidity, and to use this model to explore immunological and glutamatergic mechanisms that underlie relapse to
cocaine-taking in the context of HIV. The model will be Fischer 344 HIV-1 transgenic (Tg) rats that self-administer
vaporized cocaine via inhalation. Our overarching hypothesis is that behavioral and brain indices of relapse, i.e., cocaine-
seeking and increased glutamatergic synaptic strength, respectively, will be enhanced in Tg rats with a history of inhaled
cocaine. We will test this hypothesis and meet our project objectives by experiments grouped into two Specific Aims.
Aim 1 will establish relapse-testing in HIV-1 Tg rats. To optimize contingent cocaine-taking, we will implement
inhalation delivery of vaporized cocaine. This method emulates a delivery route and rapid brain entry of cocaine, used by
human cocaine addicts, and avoids potential immunological complications imposed by surgery and chronic indwelling
catheters needed for i.v. delivery. A cue-reactivity protocol will be used to indicate vulnerability to relapse. We
hypothesize that cue-reactivity will be greater in cocaine self-administering Tg rats than either condition alone. Aim 2
will determine the contribution of HIV-1 proteins to neuropathology associated with cocaine-seeking. Over activity
of glutamatergic AMPA receptor (AMPAR)-mediated transmission within the nucleus accumbens core (NAc) is linked to
cocaine-seeking. We reveal here that a...

## Key facts

- **NIH application ID:** 9851382
- **Project number:** 5R21DA047901-02
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** T. Celeste Napier
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,250
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851382

## Citation

> US National Institutes of Health, RePORTER application 9851382, Cocaine Abuse and HIV Comorbidity: Relapse-Related Brain Pathology. (5R21DA047901-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9851382. Licensed CC0.

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