# Calcium-related neurotoxicity of cocaine

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2024 · $438,344

## Abstract

Disfunction of the prefrontal cortex (PFC), plays a crucial role in compulsive cocaine use and addiction.
The role of glia in addition to that of neurons and vascular networks in cocaine-induced PFC dysfunction
remains elusive. In the completing R01, we showed that the neurotoxic effects of cocaine were associated
with persistent decreases in cerebral blood flow (CBF) and an elevation in intracellular calcium in cortex;
however, we did not assess the role of glia versus that of neurons on the CBF decreases. This renewal
application, "Calcium-related neurotoxicity of cocaine", will assess the effects of acute and chronic cocaine
on astrocytic Ca2+ and its role on the CBF deficits and neuronal Ca2+ increases in PFC and their association
with cocaine intake in an animal model of compulsive-like cocaine self-administration.
 Specifically, we will apply multimodality optical imaging (MOI) in combination with genetically-encoded
Ca2+ indicators to capture activities in neurons (jRGECO1a) and astrocytes (GCaMP6f) and ultrahigh-
resolution optical coherence angiography and Doppler tomography (µODT) for quantitative imaging of 3D
CBF networks in PFC of GFAP cre mice (Aim 1). We will apply chemogenetics with Designer Receptors
Exclusively Activated by Designer Drugs (DREADDs) to manipulate astrocytic Ca2+ accumulation while
assessing its consequences on acute and chronic cocaine’s vascular and neuronal effects and cocaine
intake (Aim 2, Aim 3).
 These studies will be valuable for understanding how astrocyte and neuronal networks in the PFC
interact and mediate the associated local neurovascular responses to cocaine and how they contribute to
compulsive-like drug consumption, providing knowledge to guide development of novel addiction
interventions.

## Key facts

- **NIH application ID:** 10554288
- **Project number:** 5R01DA029718-09
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Congwu Du
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $438,344
- **Award type:** 5
- **Project period:** 2012-02-15 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10554288

## Citation

> US National Institutes of Health, RePORTER application 10554288, Calcium-related neurotoxicity of cocaine (5R01DA029718-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10554288. Licensed CC0.

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