# Midbrain astrocyte energy metabolism regulating drug-evoked dopamine release and behavior

> **NIH NIH R21** · UNIVERSITY OF TEXAS SAN ANTONIO · 2021 · $195,665

## Abstract

The behavioral effects of abused substances are mediated in part by astrocyte-neuron interactions within
the mesolimbic dopamine system. Astrocytes in the ventral tegmental area (VTA) engage a local circuit to
inhibit dopamine neurons and mitigate the rewarding properties of cocaine. However, the ability for astrocytes
to regulate neuronal activity depends upon astrocyte energy metabolism. Data included in this proposal
demonstrates that ATP production by VTA astrocytes is impaired in animals that had self-administered cocaine.
Stimulating ATP production in midbrain astrocytes could therefore inhibit dopamine neurons and suppress
drug-dependent behaviors controlled by the dopamine system. This proposal will test the hypothesis that
enhancing energy metabolism in VTA astrocytes attenuates cocaine-evoked dopamine release, cocaine intake,
and the cue-induced reinstatement of cocaine seeking.
 Activating Gq signaling pathways in astrocytes promotes the production of ATP. The experiments in this
proposal will employ both chemogenetic and pharmacological approaches to selectively activate Gq signaling in
VTA astrocytes. Voltammetry recordings and behavioral assays will be utilized to determine if stimulating Gq
signaling in VTA astrocytes attenuates dopamine release to cocaine rewards (Aim 1) and elicits a reduction in
cocaine intake and the cue-induced reinstatement of cocaine seeking (Aim 2). Experiments will be performed
in the presence of glia-selective tricarboxylic acid cycle inhibitors to assess the involvement of energy
metabolism in how astrocyte Gq pathway activation affects dopamine release and behavior. Together, this
proposal will establish how energy metabolism in VTA astrocytes controls dopamine release and drug-
dependent behavior.

## Key facts

- **NIH application ID:** 10098942
- **Project number:** 1R21DA051014-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS SAN ANTONIO
- **Principal Investigator:** Matthew J. Wanat
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $195,665
- **Award type:** 1
- **Project period:** 2021-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10098942

## Citation

> US National Institutes of Health, RePORTER application 10098942, Midbrain astrocyte energy metabolism regulating drug-evoked dopamine release and behavior (1R21DA051014-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10098942. Licensed CC0.

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