# The neuropharmacology of brain activation during stages of drug abuse

> **NIH NIH DP1** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $501,000

## Abstract

Project Summary
Dopamine lies at the center of drug reward. All drugs with addiction potential increase dopamine levels in the
brain in their initial action, whether directly or indirectly. However, drugs of abuse also engage other
neurotransmitters and lead to changes in neuronal signaling affecting distributed functional circuitry. Especially
in the long term, the modulation of brain activation in response to repeated drug exposure involves
neuroadaptations not only at dopamine receptors but at multiple targets. These non-dopaminergic influences on
drug reward processing and addiction have not been extensively investigated but are key to understanding the
molecular connectome during stages of drug abuse.
For this Avenir Award, we propose to develop pharmacological positron emission tomography (PET)
simultaneously with functional magnetic resonance imaging (fMRI) as a platform to study neuroadaptations in
multi-receptor systems and their effect on functional signaling and networks in the living brain. Based on previous
work developed in our lab for imaging dopamine receptor adaptations, we will develop and validate a multi-modal
whole-brain imaging-based approach to disentangle how dopamine interacts with multiple neuroreceptors and
neurotransmitter systems. Experiments will be carried out in nonhuman primates to ensure the future
translational value of the methodologies and findings. The dynamics of multi-receptor targets will be imaged
simultaneously with fMRI at key timepoints during repeated exposure to psychostimulants to develop
neuroimaging signatures of receptor adaptations. Pharmacological blocking studies will be paired with stimulant-
induced dopamine release to unravel the differential contributions of specific pharmacological targets and related
neurotransmitter systems at various time points. Given its pivotal role in neuroplasticity, a focus will be on the
involvement of the glutamatergic system and its interplay with dopamine. The insight gained from these classes
of experiments will advance novel tools and methodology, and enable us to decipher the neuropharmacology of
brain activation during stages of drug exposure. This program has the potential to lead to the revelation of novel
drug targets for therapeutic intervention and expand our knowledge about the dynamics of neurochemistry
underlying the whole-brain functional circuitry involved in drug addiction.

## Key facts

- **NIH application ID:** 10789938
- **Project number:** 5DP1DA058360-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Christin Y. Sander
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $501,000
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10789938

## Citation

> US National Institutes of Health, RePORTER application 10789938, The neuropharmacology of brain activation during stages of drug abuse (5DP1DA058360-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10789938. Licensed CC0.

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