# HIV and opiate interactions in behavioral and anterior cingulate cortex synaptic dysfunction

> **NIH NIH F32** · VIRGINIA COMMONWEALTH UNIVERSITY · 2021 · $68,562

## Abstract

PROJECT SUMMARY.
Despite the prevalence of combination antiretroviral therapy (cART) many HIV-infected individuals experience
neurocognitive deficits, including decreased emotional processing, impulse control, and memory that interfere
with daily living. Opiates can further exacerbate HIV-1 associated neurocognitive deficits by altering neuronal
structure and function. However, HIV does not uniformly target the brain and certain regions are differentially
affected. The striatum exhibits increased dendritic pathology (varicosity formation, beading, fragmentation, and
pruning) and dendritic spine losses; whereas the anterior cingulate cortex (ACC) within the prefrontal cortex
exhibits alterations in inhibitory, but not excitatory, synaptic connections. These interneuronal deficits are
accompanied by increased depressive-like behavior. Opiates impact HIV-induced behavioral dysfunction and
we hypothesize that this is caused by disruptions to inhibitory synaptic function within the ACC resulting in a
net disruption in the excitatory/inhibitory balance of ACC pyramidal cells and overexcitation. Aim 1 will
characterize the impact of opiates on HIV-Tat-induced GABAergic neurophysiological dysfunction in ACC
pyramidal neurons using whole-cell, patch-clamp recordings and associated depressive-like behavior. Neurons
will be biocytin-filled and subsequently analyzed via 3D-reconstruction for dendritic pathology, spine density,
and inhibitory puncta. The effects of morphine and HIV-Tat on interneuronal subpopulations within the ACC will
also be assessed. Aim 2 will determine how GABA signaling impacts HIV/HIV-proteins and morphine changes
in ACC neuron ion homeostasis (Ca2+ and Cl−), structure, and survival using Cre/TdTomatoflox/flox pyramidal
neuron and Gad1-eGFP interneuron reporter mice, and human induced pluripotent stem cell (iPSC)-derived
cortical neurons. The proposed studies will further our understanding of the mechanisms by which opiates
exacerbate HIV-induced neurocognitive deficits and pathology within the ACC, and identify possible targets for
therapeutic interventions.

## Key facts

- **NIH application ID:** 10161069
- **Project number:** 1F32DA053163-01
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Sara Nass
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,562
- **Award type:** 1
- **Project period:** 2021-04-25 → 2023-04-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10161069

## Citation

> US National Institutes of Health, RePORTER application 10161069, HIV and opiate interactions in behavioral and anterior cingulate cortex synaptic dysfunction (1F32DA053163-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10161069. Licensed CC0.

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