# Neural circuit control of mesolimbic dopamine and reward

> **NIH NIH R00** · LOVELACE BIOMEDICAL & ENVIRONMENTAL RESEARCH INSTITUTE · 2021 · $249,000

## Abstract

Project Summary
Mesolimbic dopamine (DA) projections from the ventral tegmental area (VTA) to nucleus accumbens (NAc) serve
a fundamental role in goal-seeking. This neural circuit is thus central to adaptive behavior (e.g., finding food), but
can also promote psychopathologies characterized by hyper-motivation (e.g., drug abuse or obesity) or hypo-
motivation (e.g., apathy or depression), all of which exact an enormous toll on individual an economic health.
Afferent projections from numerous brain regions synapse onto VTA DA neurons to control their activity. The
current proposal aims to identify how specific inputs to DA neurons contribute to their role in motivated behaviors
and disease states. This work will focus on two primary mechanisms controlling brain DA function and reward-
related behavior. First, the lateral hypothalamus (LH) has been the subject of intense research for well over 50
years due to its fundamental role in virtually all aspects of motivated behaviors, reward processing, and reward
consumption. Second, the endocannabinoid (eCB) system is a vast signaling network that acts throughout the
brain and periphery to regulate numerous homoeostatic processes, but serves a particularly important role in
modulating brain DA function. We will use state-of-the art techniques to identify cell type- and neural circuit-
specific mechanisms by which eCB signaling controls LH influence on DA neurons and how these mechanisms
contribute to specific components of food-seeking behaviors. We will then assess similarities and differences
between the neuronal mechanisms that control food seeking versus drug-seeking by investigating their role in
the voluntary intake of amphetamine, one of the most widely abused drugs worldwide. Together, these
experiments aim to elucidate the functional overlap and distinctions between precise neural circuit mechanisms
that control adaptive versus aberrant forms of reward-driven behavior, with the ultimate goal of fundamentally
understanding motivated actions and developing safe and effective treatments for aberrant forms of reward
seeking that characterize, for example, drug abuse or obesity.

## Key facts

- **NIH application ID:** 10242228
- **Project number:** 5R00DA047432-04
- **Recipient organization:** LOVELACE BIOMEDICAL & ENVIRONMENTAL RESEARCH INSTITUTE
- **Principal Investigator:** Daniel Patrick Covey
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242228

## Citation

> US National Institutes of Health, RePORTER application 10242228, Neural circuit control of mesolimbic dopamine and reward (5R00DA047432-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242228. Licensed CC0.

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