# Methamphetamine-Alcohol Interactions and Mechanisms of Augmented Toxicity to Brain and Peripheral Organs

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $506,780

## Abstract

Project Summary/Abstract
Methamphetamine (Meth) and alcohol (EtOH) are widely co-abused but little is known about how they interact
to cause potential harm. Despite the fact that both drugs have similar effects on peripheral organs, these
peripheral effects such as inflammation are typically ignored when evaluating their individual neurobiological
effects. Moreover, Meth and EtOH also share common neurochemical underpinnings such as increased
crosstalk between glutamate neurotransmission and neuroinflammation that would predict additive or supra-
additive neurological effects when the drugs are co-abused. Thus, co-exposure to Meth and EtOH may result
in an exacerbated neurotoxic, excitotoxic, and neuroinflammatory profile. No studies however, have
systematically examined the co-exposure of Meth and EtOH, their peripheral effects, and the contribution of
their combined peripheral effects to an enhanced neurotoxicity. Therefore, the objective of the proposal is to
identify convergent peripheral and central neurobiological mechanisms involving defined brain cell types that
underlie the potential synergistic neurotoxic effects of the co-exposure to Meth and EtOH.
 The central hypothesis is that the neurotoxic effects of Meth on dopamine and 5HT terminals and neurons
are augmented and preceded by the peripheral pro-inflammatory effects of voluntary EtOH intake on the gut to
exacerbate neuroinflammation and excitotoxic glutamate neurotransmission. Specific Aim 1 will determine that
inflammation in the gut is associated with voluntary EtOH drinking and will precede and exacerbate the
neurotoxic effects of Meth. Specific Aim 2 will define the brain cell phenotype and changes in its transcriptome
related to inflammatory mediators and glutamate transmission that are affected by EtOH drinking and
subsequent exposure to Meth. The outcomes of Specific Aim 2 will guide and be integrated with Specific Aim
3 that will identify the neural mechanisms, consequences, and neurobiological significance of the co-abuse of
Meth and EtOH by assessing how glutamate neurotransmission and the excitotoxicity of Meth are influenced
by peripheral inflammation from gut. Moreover, transcription changes derived individually from astrocytes,
microglia and neurons identified in Aim 2 in response to peripheral inflammation will be examined for their
effects of glutamate neurotransmission. The long-term goal is to highlight the importance of peripheral factors
in mediating the neurobiological and behavioral effects of drugs of abuse and to develop a feasible
neuroprotective strategy that targets peripheral inflammation and mitigates the harmful biological
consequences associated with the co-abuse of Meth and EtOH.

## Key facts

- **NIH application ID:** 10148743
- **Project number:** 5R01DA042737-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Brady Atwood
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $506,780
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10148743

## Citation

> US National Institutes of Health, RePORTER application 10148743, Methamphetamine-Alcohol Interactions and Mechanisms of Augmented Toxicity to Brain and Peripheral Organs (5R01DA042737-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10148743. Licensed CC0.

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