# Subcellular Proteomics in Orbitostriatal Circuits in Incubation of Oxycodone Craving

> **NIH NIH R21** · UNIV OF MARYLAND, COLLEGE PARK · 2024 · $403,542

## Abstract

PROJECT SUMMARY/ABSTRACT
 Relapse after abstinence is a key challenge for curbing the ongoing opioid epidemic. One of the common
factors for triggering relapse is re-exposure to drug-associated cues. In rats, cue-induced oxycodone seeking
progressively increases during abstinence. The Li Lab recently published work demonstrating a critical role of
orbitofrontal cortex (OFC) in this incubation. However, molecular mechanisms in OFC underlying this incubation
are largely unknown. Moreover, OFC is interconnected with several cortical and subcortical areas. Therefore,
the distinct molecular and cellular adaptations in these OFC-associated circuits may underlie the critical role of
OFC in oxycodone relapse. Despite recent developments in next-generation sequencing technology,
transcriptomic data still tell little about the proteome state due to the complex relationship between transcription
and translation, heterogeneous subcellular distributions of proteins (e.g., soma vs. axonal terminal), and other
factors. A key limitation to profiling projection-specific proteome has been due to a lack of sufficiently sensitive
bioanalytical technologies to quantify the deep proteome in the limited amounts of material available from somas
and axonal terminals, particularly using high-resolution mass spectrometry (HRMS), the modern technology of
choice for the discovery and/or targeted analysis of the proteome. The Nemes Lab developed ultrahigh-
sensitivity HRMS platforms that enabled the quantitative characterization of neuropeptides in distinct brain areas
of the mouse and thousands of different proteins in single stem cells, and has recently begun extending these
analytical innovations to single-cell-equivalent proteomes and single neurons in the mouse. In this proposal, we
aim to profile projection-specific proteome associated with incubation of oxycodone craving by focusing on
OFCdorsal striatum (DS) projections. We will profile proteome changes in OFCDS projection neuronal
somas in OFC (Aim 1) and in OFCDS projection-specific synaptoneurosomes in DS (Aim 2) during incubation
of oxycodone craving. Overall, this proposal will bring the ultrahigh sensitive quantitative HRMS to the field of
addiction neuroscience and may provide targets for pharmacological interventions to decrease craving and
promote abstinence.

## Key facts

- **NIH application ID:** 11057120
- **Project number:** 1R21DA060380-01A1
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Xuan Anna Li
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $403,542
- **Award type:** 1
- **Project period:** 2024-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11057120

## Citation

> US National Institutes of Health, RePORTER application 11057120, Subcellular Proteomics in Orbitostriatal Circuits in Incubation of Oxycodone Craving (1R21DA060380-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11057120. Licensed CC0.

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