# Investigation of neurofunctional reorganization in cocaine addiction using mGluR5 PET and fMRI

> **NIH NIH K01** · YALE UNIVERSITY · 2020 · $179,724

## Abstract

PROJECT SUMMARY/ABSTRACT
 Cocaine use disorder (CUD) remains a significant public health concern that is resistant to current
treatments and associated with neurobiological alterations impacting multiple cognitive functions. Challenges
to treating CUD include an imbalance in neurofunctional systems that ‘re-wire’ the brain such that appetitive
and habitual processes direct maladaptive decision-making and behavior. The proposed research aims to
provide insight into this reorganized circuitry in CUD by investigating neurofunctional systems related to
glutamate and functional brain networks.
 The metabotropic glutamate 5 receptor (mGluR5) is a postsynaptic receptor involved in neuroplastic
mechanisms, and associated with modulating the acquisition and persistence of addictive behavior in CUD.
Studies of mGluR5 in CUD demonstrate a widespread reduction in availability during early abstinence;
however, less is known regarding mGluR5 availability in current users, and relationships to reorganized brain
circuitry underlying cognitive functioning. Resting-state and task-based (e.g., response inhibition) performance
involve coordinated activity in known functional brain networks and alterations in connectivity patterns in CUD
lend insight in a reorganization of circuitry (e.g., fronto-parietal systems) central to addictive behaviors. This
application proposes to investigate the distribution of mGluR5 through PET imaging using the highly-selective
radioligand [18F]FPEB (Aim 1), and functional network activity at resting-state and related to response inhibition
using a Go/NoGo task during fMRI (Aim 2) in currently-using individuals with CUD and matched healthy
comparison participants. Additional sophisticated analytics (e.g., independent component analysis) will be used
to integrate these multi-modal data (Aim 3), providing novel insight into the relationship between these
neurofunctional systems in CUD.
 This program of research and training will integrate state-of-the-art biomedical imaging facilities at the
Yale School of Medicine. The mentorship team consists of internationally renowned experts in addiction
psychiatry, computational statistics and molecular neuroscience. The program will provide the candidate with
the requisite skills and experience to become an independent investigator in the field of addictions
neuroscience. In pursuit of this goal, the candidate proposes to undertake further training in three primary
areas: (i) the conduct of human PET research protocols and image analysis methods; (ii) sophisticated
statistics toward the integration of multi-modal neuroimaging data; and (iii) the molecular neuroscience of
addictions psychiatry. The opportunities afforded by this award would enable the candidate to embark on a
comprehensive, structured 5-year program of training and research designed to develop an expertise in
innovative neurobiological research methods toward a career as an independent addictions investigator.

## Key facts

- **NIH application ID:** 9980321
- **Project number:** 5K01DA042998-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Patrick D Worhunsky
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $179,724
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980321

## Citation

> US National Institutes of Health, RePORTER application 9980321, Investigation of neurofunctional reorganization in cocaine addiction using mGluR5 PET and fMRI (5K01DA042998-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9980321. Licensed CC0.

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