# Imaging dopamine receptor adaptations and signaling pathways with combined PET/fMRI-Supplement

> **NIH NIH R00** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $11,613

## Abstract

Project Summary
Drug addiction is a complex neuro-behavioral disorder, involving pharmacological, psychological and genetic
influence. The dopamine receptor system plays a highly relevant role for mechanisms underlying reward and
addiction. At the synaptic level, sensitization is mediated through dynamic mechanisms, such as receptor
internalization; at the whole-brain level, adaptation is reflected through dynamic changes in brain signaling.
These dynamic changes, and how drug exposure or treatment can alter them, are still not well understood in
vivo but are a critical step towards improving treatment options and outcomes for substance abuse and related
psychiatric disorders. The goal of this grant is to apply in vivo with multi-modal imaging in order to investigate
how specific pharmacological interventions and stimulant drugs of abuse modulate receptor adaptation
mechanisms of the dopamine receptor system, and test novel approaches to prevent such adaptation
mechanisms.
 State-of-the-art integrated positron emission tomography (PET) with functional magnetic resonance
imaging (fMRI) will be used to image receptor trafficking dynamics using drugs that are known to induce
receptor internalization at D2/D3 dopamine receptors, and then measure these adaptations for stimulants
drugs of abuse. Non-human primates will be imaged to establish dynamic relationships between receptor
occupancy (PET) and functional activation (fMRI). Together with biophysical modeling, quantification of
receptor trafficking rates and their influence on functional signaling will be quantified. Finally, the involvement
of the glutamate receptor system will be tested as an approach to modulate or prevent receptor trafficking as
induced by drugs of abuse. This approach will help unravel the action of drugs targeted at the dopamine
systems and their role in the neurobiological evolution of the development, maintenance and eventual
prevention and treatment of drug addiction.

## Key facts

- **NIH application ID:** 10399849
- **Project number:** 3R00DA043629-04S1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Christin Y. Sander
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $11,613
- **Award type:** 3
- **Project period:** 2021-06-09 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399849

## Citation

> US National Institutes of Health, RePORTER application 10399849, Imaging dopamine receptor adaptations and signaling pathways with combined PET/fMRI-Supplement (3R00DA043629-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10399849. Licensed CC0.

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