Award
National Institute on Drug Abuse 5F31DA064363-02
Dopaminergic modulation of NMDA receptor signaling in the Nucleus Accumbens
Recipient
University of Colorado Denver, Aurora, CO
Award Amount
$41,846.00
Ceiling
$41,846.00
Awarded
July 23, 2026
Identifier
5F31DA064363-02
This award funds research to understand how dopamine receptor signaling modulates NMDA receptor activity in the Nucleus Accumbens, a key brain region involved in substance use disorders. The study aims to elucidate mechanisms of dopamine-glutamate interactions using advanced neuroscience techniques, potentially informing new strategies for addiction research.
Description
Understanding how dopaminergic signaling regulates neuronal activity is essential to understanding how brain reward circuits become altered as a result of chronic drug use. Dopamine receptor signaling importantly tunes the activity of glutamatergic NMDA receptors to regulate neuronal excitability, yet the exact mechanisms underlying dopamine receptor modulation of NMDA receptors remains unclear. A better understanding of dopamine-glutamate interactions has the potential to identify new strategies for investigating substance use disorders. Alterations in both dopamine (DA) and glutamate signaling in the Nucleus Accumbens (NAc) are thought to play a key role in substance use disorders and addiction. DA regulates NAc circuit activity by modulating glutamatergic transmission and receptor activity, however, the precise mechanisms remain unclear. Synaptic plasticity and regulation of intracellular excitability is primarily attributed to the functions of glutamatergic NMDA receptors (NMDARs). How dopamine receptors regulate NMDAR activity and how this differs between synaptic connections in accumbal circuitry remain important questions. This proposal will utilize ex vivo slice electrophysiology in combination with optogenetics and iontophoresis in transgenic mouse lines to investigate the synapse specificity and intracellular signaling mechanisms underlying DA receptor regulation of NMDAR current in both D1 and D2 type dopamine receptors. Understanding the synergistic role of D1 and D2 receptor signaling in regulating glutamate transmission and receptor activity in the NAc is a critical step in the investigation of both motivation and the dysfunctions that arise in this system after exposure to drugs of abuse.