# Imaging Synaptic Density in the Opiate Addicted Brain using 11C UCB J PET

> **NIH NIH R21** · YALE UNIVERSITY · 2020 · $251,250

## Abstract

Project Summary
A major goal of modern addiction research is to understand the neural adaptations that underlie the chronic,
maladaptive and, for many, treatment-refractory behaviors produced by drugs of abuse, including opiates.
Considerable optimism exists in this regard, as powerful preclinical tools and well-established animal models
have dramatically advanced our understanding of the molecular and cellular mechanisms of opiate-related
plasticity [1]. Nonetheless, a considerable gap remains in the clinical-translational testing and validation of such
preclinical findings in human opiate addiction.
In seminal preclinical studies nearly 20 years ago, Robinson & Kolb [3-5] demonstrated enduring decreases in
synaptic (i.e., dendritic spine) density in both the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC)
of rodents despite sustained (0-4 weeks) abstinence from chronic opiate administration. Their findings were
compelling and suggested an important pathophysiological mechanism – persistent aberrant structural synaptic
plasticity – whereby opiates might produce the chronic, recalcitrant behaviors (e.g., craving, compulsive use, and
relapse) so seemingly ‘hard-wired’ in those suffering from the disorder.
Our group has developed a novel radiotracer, 11C-UCB-J, for imaging synaptic density in the living human brain
using positron-emission tomography (PET) [62, 63]. Thus, the current exploratory/development (R21)
application seeks to apply this breakthrough methodology to explore whether observations of decreased
synaptic density in the NAc and mPFC (and increases in orbitofrontal cortex) of rodents are recapitulated in
abstinent opiate use disorder (OD) humans.
If achieved, the current study would have a major impact, providing powerful clinical-translational support for
aberrant brain structure at the synaptic level, setting the stage for future studies of the relationship of such
aberrant synaptic density to risk for relapse, opiate-related behaviors and clinical prognosis/outcome.

## Key facts

- **NIH application ID:** 9853003
- **Project number:** 5R21DA046030-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** GUSTAVO Adolfo ANGARITA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $251,250
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853003

## Citation

> US National Institutes of Health, RePORTER application 9853003, Imaging Synaptic Density in the Opiate Addicted Brain using 11C UCB J PET (5R21DA046030-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853003. Licensed CC0.

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