# Encoding dopamine signals in the mesolimbic system

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $349,875

## Abstract

Project Summary
Alterations in the dopamine system underlie a variety of psychiatric disorders including drug addiction. In
order to understand how these alterations arise, it is necessary to first understand the basic mechanisms
that regulate how dopamine mediates transmission. One of the key brain regions where many drugs of
abuse, including cocaine, mediate their rewarding and reinforcing properties is within the nucleus
accumbens and dorsal striatum. Despite a wealth of literature examining the interaction between cocaine
and the dopamine system in striatal circuits and an understanding of the cellular and molecular singling
pathways of dopamine receptors, relatively little is known in regards to how the synaptic release of
dopamine leads to the activation of post-synaptic receptors, where those receptors are located and how
cocaine alters transmission and the synaptic activation of dopamine receptors. To address this, the current
proposal will use a novel approach to examine the location and synaptic activation of D2 receptors and
GABAA receptors in medium spiny neurons of the dorsal striatum and nucleus accumbens. By
simultaneously imaging D2-receptors while electrophysiologically measuring their synaptic activation by
dopamine the application will determine how D2-receptors encode nigrostriatal and mesolimbic dopamine
signals. Additionally, the proposal aims to examine if the synaptic corelease of GABA and dopamine are
differentially regulated and how cocaine exposure alters receptor synaptic activation. These experiments
will test the central hypothesis that striatal dopamine transmission occurs in a point-to-point synaptic
manner. The significance of this work will be to determine how dopamine receptors across striatal regions
encode dopamine release and how this is altered following exposure to drugs of abuse. The proposed
studies are expected to be significant in that insights in to the specific mechanisms that regulate dopamine
transmission, GABA co-transmission and how they are altered by exposure to cocaine are expected to
directly lead to testable hypothesis regarding the dysregulations in this system that occur as a result of
chronic drug abuse and addiction.

## Key facts

- **NIH application ID:** 10112867
- **Project number:** 5R01DA035821-09
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Christopher Peter Ford
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $349,875
- **Award type:** 5
- **Project period:** 2013-08-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112867

## Citation

> US National Institutes of Health, RePORTER application 10112867, Encoding dopamine signals in the mesolimbic system (5R01DA035821-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10112867. Licensed CC0.

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