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Proteomes. 2018 Sep 23;6(4). pii: E35. doi: 10.3390/proteomes6040035.

Granulocyte-Colony-Stimulating Factor Alters the Proteomic Landscape of the Ventral Tegmental Area.

Author information

1
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. nicholasmervosh@gmail.com.
2
Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. nicholasmervosh@gmail.com.
3
Yale/NIDA Neuroproteomics Center, New Haven, CT 06511, USA. rashaun.wilson@yale.edu.
4
Yale/NIDA Neuroproteomics Center, New Haven, CT 06511, USA. navin.rauniyar@yale.edu.
5
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. rebecca.hofford@mssm.edu.
6
Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. rebecca.hofford@mssm.edu.
7
Department of Pharmacology, Vanderbilt Center for Addiction Research, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. gunes.kutlu@vanderbilt.edu.
8
Department of Pharmacology, Vanderbilt Center for Addiction Research, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. erin.calipari@vanderbilt.edu.
9
Yale/NIDA Neuroproteomics Center, New Haven, CT 06511, USA. tukiet.lam@yale.edu.
10
Department of Molecular Biophysics & Biochemistry, New Haven, CT 06510, USA. tukiet.lam@yale.edu.
11
Yale MS & Proteomics Resource, New Haven, CT 06510, USA. tukiet.lam@yale.edu.
12
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. drew.kiraly@mssm.edu.
13
Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. drew.kiraly@mssm.edu.
14
Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. drew.kiraly@mssm.edu.

Abstract

Cocaine addiction is characterized by aberrant plasticity of the mesolimbic dopamine circuit, leading to dysregulation of motivation to seek and take drug. Despite the significant toll that cocaine use disorder exacts on society, there are currently no available pharmacotherapies. We have recently identified granulocyte-colony stimulating factor (G-CSF) as a soluble cytokine that alters the behavioral response to cocaine and which increases dopamine release from the ventral tegmental area (VTA). Despite these known effects on behavior and neurophysiology, the molecular mechanisms by which G-CSF affects brain function are unclear. In this study mice were treated with repeated injections of G-CSF, cocaine or a combination and changes in protein expression in the VTA were examined using an unbiased proteomics approach. Repeated G-CSF treatment resulted in alterations in multiple signaling pathways related to synaptic plasticity and neuronal morphology. While the treatment groups had marked overlap in their effect, injections of cocaine and the combination of cocaine and G-CSF lead to distinct patterns of significantly regulated proteins. These experiments provide valuable information as to the molecular pathways that G-CSF activates in an important limbic brain region and will help to guide further characterization of G-CSF function and evaluation as a possible translational target.

KEYWORDS:

addiction; cocaine; cytokine; neuroimmune; ventral tegmental area

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

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