# Dopamine Neuronal Microcircuits Controlling Methamphetamine Seeking Behavior

> **NIH NIH K99** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $149,666

## Abstract

Project Summary/Abstract
This proposal is submitted to support the transition of Dr. Dominguez-Lopez from a mentored trainee to an
independent investigator in the neurobiology of drug addiction, specifically studying the dopamine
microcircuits controlling drug-seeking behavior. Dr. Dominguez-Lopez will work under the mentorship of Dr.
Mary Kay Lobo at the University of Maryland School of Medicine (UMSOM), investigating the role of dopamine
neurotransmission in the ventral tegmental area (VTA) in methamphetamine (METH) self-administration
behavior. Dr. Lobo is a recognized expert in motivated behavior and dopamine neurotransmission in the
context of drug abuse. Dr. Lobo’s laboratory combines mouse models of drug self-administration with
mitochondrial metabolism, molecular biology, genetics, and immunocytochemistry, providing a dynamic
environment for Dr. Dominguez-Lopez to become an experienced scientist. The submitted proposal
incorporates scientific training in methodologies to study mitochondrial metabolism, transcriptional analysis,
bioinformatics, and genetic labeling of active neuronal populations. The applicant will be receiving training in
educational methods, scientific writing, grant preparation, and other skills necessary to become an
independent brain research scientist from an underrepresented group. The proposed program includes
mentoring interactions with Drs. Joseph Cheer, Seth Ament, Brian Polster, faculty members of UMSOM, and
Dr. Marisela Morales from NIDA IRP. In addition, Dr. Rajeshwar Awatramani from Northwestern University in
Chicago will be a consultant in this project. The short-term objective of this proposal is to enhance Dr.
Dominguez-Lopez’s knowledge of mitochondrial metabolism and single-cell transcriptomics applied to
dopaminergic circuits. In the long-term, this will enable Dr. Dominguez-Lopez to secure protected time for
training and research activities, establish new collaborations, and pursue his novel independent research
resulting in competitive grant proposals. Data obtained by Dr. Dominguez-Lopez indicates that prolonged
METH self-administration in mice produces a decrease of dopamine neurons in the VTA, decreases dopamine
cell excitability, increases mitochondrial oxygen consumption rate, and decreases levels of glutathione. These
observations are concurrent with increased drug-seeking behavior. This research proposal expands on those
findings to identify metabolic and molecular characteristics in dopamine circuits that provide resistance or
vulnerability to METH exposure. The central hypothesis is that a subpopulation of VTA dopamine neurons is
responsible for METH-seeking behavior, forming a microcircuit resistant to mitochondrial oxidative stress
induced by chronic METH exposure. The proposed aims are 1) Identifying VTA dopamine microcircuits
encoding METH-seeking behavior and 2) Metabolic characteristics of VTA dopamine neurons encoding
METH-seeking behavior. Identifying the specific brain circuits resp...

## Key facts

- **NIH application ID:** 10591238
- **Project number:** 3K99DA049719-03S1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Sergio Dominguez Lopez
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $149,666
- **Award type:** 3
- **Project period:** 2021-07-19 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10591238

## Citation

> US National Institutes of Health, RePORTER application 10591238, Dopamine Neuronal Microcircuits Controlling Methamphetamine Seeking Behavior (3K99DA049719-03S1). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/10591238. Licensed CC0.

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