# Neuroimmune modulation of neuronal function during cocaine conditioning

> **NIH NIH R21** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $211,875

## Abstract

Project Summary
Pathological substance use disorders are a public health crisis leading to tremendous morbidity and mortality
for afflicted patients and incalculable costs to society at large. Addiction to cocaine and other psychostimulants
accounts for a significant proportion of this burden of disease, and treatment of these patients is currently
limited by the lack of any FDA-approved pharmacotherapies. Despite significant advances in our
understanding of the dopaminergic, glutamatergic, and intracellular signaling cascades altered in models of
stimulant use disorders, efforts to develop medications aimed at treating stimulant use disorder have been
unsuccessful. There is a growing appreciation for the role of neuroimmune interactions in normal brain function
and plasticity as well as in the pathophysiology of neuropsychiatric diseases. Microglia, the resident immune
cells of the CNS, interact with neurons, prune synapses, and produce neurotrophic factors that can alter
synaptic plasticity and behavior. We have recently identified granulocyte-colony stimulating factor (G-CSF) as
a cytokine that is increased in blood and brain following prolonged cocaine. Systemic injections of G-CSF
enhance the formation of conditioned place preference and enhance motivation to self-administer cocaine.
Additionally, G-CSF potentiates cocaine induction of the immediate early gene c-Fos and enhances dopamine
release from the ventral tegmental area into the nucleus accumbens (NAc). Interestingly, the receptor for G-
CSF is expressed exclusively on microglia in the NAc. In this proposal we will utilize cutting-edge in vivo
imaging technology to directly visualize and interrogate the effects of this microglial modulator on patterns of
neuronal activity that encode cocaine administration and seeking. In Aim 1 we will record calcium signals in D1
and D2 expressing medium spiny neurons in the NAc of animals treated with G-CSF or vehicle during active
cocaine self-administration or during a drug seeking task. Given that the D1 and D2 expressing populations of
neurons have been shown to have opposing effects on encoding rewarding stimuli, these experiments will
provide crucial information as to how G-CSF is shifting the balance of patterns of neural activity between these
two discrete cell populations. In Aim 2, we will test the causal nature of G-CSF signaling through microglia by
using a transgenic mouse model that deletes the G-CSF receptor exclusively in microglia and measure
behavioral and neural circuit changes. Together, these experiments will characterize the neural circuit changes
induced by G-CSF signaling through microglia and elucidate the mechanisms by which microglial signaling
controls cocaine-associated behavior.

## Key facts

- **NIH application ID:** 10015251
- **Project number:** 5R21DA049568-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Drew Kiraly
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $211,875
- **Award type:** 5
- **Project period:** 2019-09-15 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10015251

## Citation

> US National Institutes of Health, RePORTER application 10015251, Neuroimmune modulation of neuronal function during cocaine conditioning (5R21DA049568-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10015251. Licensed CC0.

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