期刊
PROTEOMES
卷 6, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/proteomes6040035
关键词
cocaine; addiction; cytokine; neuroimmune; ventral tegmental area
资金
- Yale/NIDA Neuroproteomic Center Grant from NIDA [P30-DA018343]
- NIDA [DA044308, DA042111]
- Brain and Behavior Research Foundation
- Whitehall Foundation
- Edward Mallinckrodt Jr. Foundation
- Friedman Brain Institute
- Leon Levy Foundation
- Seaver Family Foundation
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.
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