# In vivo calcium imaging during appetitive learning in HIV Tat transgenic mice exposed to cannabis

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $194,375

## Abstract

Project Summary
In the context of human immunodeficiency virus (HIV) infection, cannabis use is an important topic and is the
most commonly used drug among people living with HIV (PWH), despite the success of combined antiretroviral
therapy (cART). Cannabis use is known to alleviate common symptoms and complications in PWH on cART,
including chronic pain, nausea, and anxiety/depression, but contradicting results have been reported for
cannabis use on cognitive performance. As cART does not cross the blood brain barrier the prevalence of mild
to moderate forms of cognitive impairments, known as HIV-1-associated neurocognitive disorders (HAND),
remain high (50%). Brain regions that are specifically vulnerable to HIV include the frontostriatal system,
involving deficits in learning, memory and reward-related behaviors. HIV-1 proteins released by HIV-1 infected
cells, including the transactivator of transcription (Tat) protein, are known to play a major role in the underlying
HAND neuropathology, including lasting changes in neuronal excitability, inflammatory processes, and synaptic
communication. Nevertheless, it is not clear how neuronal activity is altered by HIV Tat during learning while an
animal is performing a behavioral task, i.e in the context of reward. With the establishment of in vivo calcium
imaging, it has been shown that dorsomedial prefrontal cortex neurons that project to the nucleus accumbens
(PFC-NAc) increase their neuronal activity after successful appetitive discrimination learning. The goal of the
proposed study is to determine cannabis-induced changes on neuronal activity in a neuroHIV mouse model
during performance of a behavioral reward-related learning task and its relation to the endocannabinoid (eCB)
system. To achieve this goal, we will make use of a well-established mouse model of neuroHIV and propose two
aims. Aim 1 will determine how CBD:THC ratios alter prefrontal neuronal activity in HIV Tat transgenic male and
female mice performing a reward-related learning task. Animals will undergo viral injections to visualize in vivo
calcium activity in PFC-NAc neurons and drug administration starts with behavioral assessment. Head-fixed
mice will be trained to perform a Pavlovian conditioning task, that presents reward-predictive cues, and tests
animal’s ability to learn to discriminate between a conditioned stimulus that predicts sucrose reward (CS+) but
not the other (CS-). Neuronal activity will be recorded throughout training and compared before and after
learning. Aim 2 will determine the effect of different CBD:THC ratios (1:15, 1:1, 15:1) on the eCB system and
pathology in relation to appetitive discrimination learning in HIV Tat transgenic mice. Immunohistochemistry will
be used to assess cell-specific localization of cannabinoid-like receptors (CB1R, CB2R, GPR55) and catabolic
enzymes (FAAH, MAGL) on neurons, astrocytes, and microglia in the dorsomedial PFC and NAc; (non-)eCB
ligands (e.g. AEA, 2-AG, AA, OEA, PEA) w...

## Key facts

- **NIH application ID:** 10806213
- **Project number:** 5R21DA057871-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Sylvia Fitting
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $194,375
- **Award type:** 5
- **Project period:** 2023-03-15 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10806213

## Citation

> US National Institutes of Health, RePORTER application 10806213, In vivo calcium imaging during appetitive learning in HIV Tat transgenic mice exposed to cannabis (5R21DA057871-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10806213. Licensed CC0.

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