# Glial Integration of Survival Circuits

> **NIH NIH K00** · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · 2020 · $86,378

## Abstract

PROJECT ABSTRACT
 Psychostimulant abuse is a major public health concern, yet no FDA-approved therapies
exist. 3,4-methylenedioxypyrovalerone (MDPV) is a type of `bath salt' that is ten times stronger,
but mechanistically similar, to cocaine. This psychostimulant has powerful reinforcing effects
that manifest as escalating self-administration and relapse following abstinence. Chemokines,
chemotactic inflammatory proteins, are dysregulated in cocaine users. The chemokine receptor-
ligand pair CXCR4-CXCL12 in particular has been linked to psychostimulant use. Human
cocaine users and rodent models have heightened plasma CXCL12 levels, and CXCL12
potentiates the dopaminergic and hyperlocomotive effects of cocaine. Through mastery of
rodent self-administration, I have expanded my technical repertoire and revealed that
AMD3100, a CXCR4 antagonist, decreases cocaine and MDPV-induced hyperlocomotion, self-
administration, and conditioned place preference, reflecting a reduction in the reinforcing effects
of MDPV. Moreover, repeated MDPV increases CXCL12 and CXCR4 mRNA in the ventral
tegmental area and decreases dendrite morphometrics in the nucleus accumbens (NAC) core.
These findings strongly implicate that CXCR4 modulation alters the reinforcing and neuroplastic
effects of MDPV. F99 phase research studies will extend these findings by measuring dendrite
morphology and neuroelectrical properties of the NAC core following AMD3100 treatment and
MDPV self-administration sessions. Structural plasticity will be examined using a Golgi-Cox
stain followed by computer-assisted neuron reconstruction. Whole cell patch clamp will be
mastered to examine NAC core electrical property dynamics and glutamatergic drive. Learning
these electrophysiological techniques will expanding my technical repertoire, elucidate the
effects of MDPV self-administration on structural neuroelectrical plasticity in the NAC core, and
promote my ultimate career goal of becoming an independent neuroscience researcher. The
results of these studies may reveal modulation of the receptor-ligand CXCR4-CXCL12 system
as a therapeutic target for treatment of psychostimulant addiction. Finally, the proposed project
will provide a foundation upon which a postdoctoral research focus on substance abuse can be
built, in preparation for a career as an independent neuroscience researcher.

## Key facts

- **NIH application ID:** 9923469
- **Project number:** 7K00NS105218-03
- **Recipient organization:** NATHAN S. KLINE INSTITUTE FOR PSYCH RES
- **Principal Investigator:** Chicora F Oliver
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $86,378
- **Award type:** 7
- **Project period:** 2018-07-31 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923469

## Citation

> US National Institutes of Health, RePORTER application 9923469, Glial Integration of Survival Circuits (7K00NS105218-03). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/9923469. Licensed CC0.

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