# Ventral Tegmental Area GABA Neurons: Plasticity & Opiate Receptors at InhibitoryInputs

> **NIH NIH R15** · BRIGHAM YOUNG UNIVERSITY · 2024 · $454,500

## Abstract

Project Summary:
Over 22 million people need treatment for illicit drug/alcohol abuse in the U.S. (SAMHSA survey), costing
the government $468 billion per year in related expenses. After alcohol and smoking, opiates are the
leading cause for those admitted to substance abuse treatment programs. Currently, there is an opiate
crisis throughout the US. Opiate abuse resulted in an exponential increase in synthetic opiate-caused
deaths from ~3,000 in 2012 to almost 30,000 in 2017 (NIDA website: Aug. 2018). However, individuals
attempting to overcome opiate as well as other addictions often relapse. Therefore, a better understanding
of the reward circuit, in addition to a complete understanding of opiate targets in the reward circuit is
essential. Here we propose to investigate the impact of morphine on a novel form of synaptic plasticity of
inhibitory inputs as well as excitatory inputs onto inhibitory GABA cells in the ventral tegmental area
(VTA), the brain’s reward center. Within the VTA, dopamine-containing cells are involved in motivation and
reward. Reward is an essential component of survival, mediated by increased dopamine release from the
VTA. Drugs of abuse dramatically enhance dopamine levels beyond normal rewarding behaviors, but also
cause synaptic modifications on VTA cells, leading to the diseased state of addiction. While known that
illicit drugs cause modifications to dopamine cell synapses, neither normal synaptic plasticity of GABA
neurons nor how opiates alter GABA neuron activity is completely known. This, despite the fact that GABA
neurons are involved in vivo in both the perception and associative learning of reward. Therefore, this role in
reward makes VTA GABA cells nearly as important as DA cells to investigate. As opiates mediate non-pain
related actions in the VTA, our findings will paint a clearer picture of neurocircuit adaptations caused by
opiates and provide a basis for examining the effect of other drugs of abuse on GABA plasticity. The long-
term goal is to understand normal physiology and morphine-induced modification of inputs to VTA GABA
cells. We hope examining opiate-induced VTA neuroadaptations provides a more comprehensive solution
in our efforts to reverse addiction. We hypothesize that unique VTA GABA cells that express distinct forms of
plasticity that will correlate differentially to VTA GABA neurons that are either projecting or interneurons. We
further hypothesize that excitatory and inhibitory forms of GABA cell plasticity will be maladaptively altered by
chronic, but not acute, morphine exposure. We also will examine the potential impact of VTA GABA cell plasticity
based on the cells unique projections and impact on DA cells. Collectively, this data will provide a better
framework of GABAergic circuit role in reward, and morphine effect on synaptic modifications. We will examine
this hypothesis using single cell electrophysiology, Retrobeads, rabies virus, optogenetics, and single cell
PCR, etc. As cur...

## Key facts

- **NIH application ID:** 10974737
- **Project number:** 2R15DA049260-02A1
- **Recipient organization:** BRIGHAM YOUNG UNIVERSITY
- **Principal Investigator:** JEFFREY G EDWARDS
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $454,500
- **Award type:** 2
- **Project period:** 2020-09-30 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10974737

## Citation

> US National Institutes of Health, RePORTER application 10974737, Ventral Tegmental Area GABA Neurons: Plasticity & Opiate Receptors at InhibitoryInputs (2R15DA049260-02A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10974737. Licensed CC0.

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