# High-Throughput Whole-Brain Screening for Drug-Induced Chemical Imbalance in the Brain

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $197,344

## Abstract

Project Summary Abstract:
Repeated exposure to a drug of abuse induces alterations in neuronal activity and neuroplastic changes in
multiple brain areas and circuits related to reward, impulse control and affect. These widespread changes
contribute to multiple behavioral alterations. Despite differing in their molecular targets, different drugs cause
common alterations in the brain. Increasing our knowledge of the impact of drugs of abuse on multiple brain
regions and circuits is crucial to better understand the mechanisms that mediate the transition from drug use to
addiction and facilitate the development of novel treatment.
We hypothesize that phencyclidine induces neurotransmitter switching in more than just one brain region and
that different categories of drugs induce a shared transmitter switch that is relevant for the transition from drug
intake to addiction. To test these hypotheses we are developing genetic mouse models to facilitate high-
throughput, whole-brain screening of transmitter switching involving GABA and glutamate. The current assays
of transmitter switching involve time consuming sectioning of a single parts of the brain, staining sections and
stereology, putting whole-brain analysis out of reach.
The combination of genetically encoded fluorescent reporter proteins, brain clarification, light sheet microscopy
and whole-brain automatic image analysis will speed analysis and accelerate understanding of the role of
transmitter switching in drug-induced neuroplasticity and drug-induced behavioral alteration. These tools will be
used to determine whether two different substances of abuse that have distinct targets in the brain, PCP and
methamphetamine (METH), induce NTS in multiple brain regions and whether some PCP- and METH-induced
NTS are the same.

## Key facts

- **NIH application ID:** 10131176
- **Project number:** 5R21DA050821-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** NICHOLAS CANADAY SPITZER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $197,344
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131176

## Citation

> US National Institutes of Health, RePORTER application 10131176, High-Throughput Whole-Brain Screening for Drug-Induced Chemical Imbalance in the Brain (5R21DA050821-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10131176. Licensed CC0.

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