# Relationship of Brain Ethanol Oxidation with Behavior

> **NIH NIH R21** · YALE UNIVERSITY · 2021 · $198,906

## Abstract

Abstract
When people drink, the ethanol can provide energy for the brain, and that supply increases with chronic, heavy
exposure in rats and humans. The energy derives partly from acetate that is generated hepatically and
released into the blood, which is then carried to the brain. However, ethanol can also be oxidized inside the
brain. This process contributes to behavioral effects of ethanol, including the locomotor reduction seen with
ethanol administration in rats, and there may be relationships between vulnerability to alcohol abuse and how
brain and systemic ethanol metabolism occurs, even though both processes are toxic. We propose to quantify
brain ethanol oxidation, including a way to assess rates of flow through catalase relative to total brain ethanol
oxidation. We will examine how brain ethanol metabolism interacts with gender and chronic ethanol exposure
to affect behavior following acute and chronic ethanol exposure.
Catalase is believed to dominate brain ethanol oxidation. We propose to obtain measures of locomotor activity
and metabolism with and without catalase inhibition to quantify the portion of brain ethanol oxidation that flows
through catalase. There is strong reason to believe that male and female rats will differ with respect to enzyme
activity, metabolism, and behavioral responses to ethanol, including following chronic ethanol exposure, so we
will study male and female rats and use vapor chambers to achieve daily exposure. Other enzymes,
cytochrome P450, specifically the Cyp2e1 isoform, and possibly to a limited extent brain alcohol
dehydrogenase, may also contribute to brain ethanol oxidation. However, we are focusing the resources of
this R21 project on (1) establishing the enzyme procedure in the context of the metabolic rate measurements
as related to behavior, (2) determining how much of the exposure-induced increase in brain ethanol oxidation
is due to catalase versus other enzymes, and (3) assessing how metabolism and exposure interact to affect
behavior differences by sex.
The project relates to human health because men and women are known to be affected differently by ethanol
for multiple reasons, and this project may illuminate metabolic mechanisms that can contribute to these sex
differences. The results will ultimately provide information about enzyme targets of potential importance to
prevent the neurotoxic effects of ethanol that may be related to vulnerability to alcohol abuse and dependence.

## Key facts

- **NIH application ID:** 10244983
- **Project number:** 5R21AA028628-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Graeme F Mason
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $198,906
- **Award type:** 5
- **Project period:** 2020-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244983

## Citation

> US National Institutes of Health, RePORTER application 10244983, Relationship of Brain Ethanol Oxidation with Behavior (5R21AA028628-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10244983. Licensed CC0.

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