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Granulocyte-Colony Stimulating Factor reduces cocaine-seeking and downregulates glutamatergic synaptic proteins in medial prefrontal cortex
Open accessPreprint — published as 10.1523/jneurosci.1452-20.2020 · Paper page
Abstract
Background: Psychostimulant use disorder is a major public health issue, and despite the scope of the problem there are currently no FDA approved treatments. There would be tremendous utility in development of a treatment that could help patients both achieve and maintain abstinence. Previous work from our group has identified granulocyte-colony stimulating factor (G-CSF) as a neuroactive cytokine that alters behavioral response to cocaine, increases synaptic dopamine release, and enhances cognitive flexibility. Here, we investigate the role of G-CSF in affecting extinction and reinstatement of cocaine-seeking and perform detailed characterization of its proteomic effects in multiple limbic substructures. Methods: Sprague-Dawley rats were injected with PBS or G-CSF during (1) extinction or (2) abstinence from cocaine self-administration, and drug seeking behavior was measured. Quantitative assessment of changes in the proteomic landscape in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were performed via data-independent acquisition (DIA) mass spectrometry analysis. Results: Administration of G-CSF during extinction accelerated the rate of extinction, and administration during abstinence attenuated cue-induced cocaine-seeking. Analysis of global protein expression demonstrated that G-CSF regulated proteins primarily in mPFC that are critical to glutamate signaling and synapse maintenance. Conclusion: Taken together, these findings support G-CSF as a viable translational research target with the potential to reduce drug craving or seeking behaviors. Importantly, recombinant G-CSF exists as an FDA-approved medication which may facilitate rapid clinical translation. Additionally, using cutting-edge multi-region discovery proteomics analyses, these studies identify a novel mechanism underlying G-CSF effects on behavioral plasticity.
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Global quantification of mammalian gene expression control
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“4 or lower (Ghazalpour et al., 2011; Schwanhäusser et al., 2011; Kumar et al., 2016).”
BackgroundInfluentialPsychostimulant drugs for cocaine dependence
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Metadata
- Authors
- Hofford, R. S., Euston, T. J., Wilson, R. S., Meckel, K. R., Peck, E. G., Godino, A., Landry, J. A., Calipari, E. S., Lam, T. T., & Kiraly, D. D.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Yale University (US)
- Wake Forest University Health Sciences (US)
- Vanderbilt University (US)
- Corresponding author
- Kiraly, Drew D.
- ORCID
- Venue
- Journal of Neuroscience
- Publisher
- openRxiv
- Published
- 2020-02-18
- Volume
- 41
- Issue
- 7
- Pages
- 1553-1565
- ISSN
- 0270-6474 (ISSN-L)
- PMC
- PMC7896012
- OpenAlex
- W3114748821
- Cited by
- 17
- References
- 2
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 1
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Brain and Behavior Research Foundation
- Ohio Department of Development
- Yale University
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (1s10od019967-01, 1s10od018034-01, 5dp1da048931-05, DA-018343)
- National Institute on Drug Abuse (042111, DA042111, DA048931, K08DA044308, K99DA042111, DA049568, DP1-DA048931, R00DA042111, DA044308, DP1DA051551, R21DA049568, DA 018343, T32DA041349, P30DA018343)
- National Institute of Neurological Disorders and Stroke (R03NS111493)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- granulocyte colony-stimulating factor, cocaine seeking, cocaine self-administration, extinction, reinstatement, cocaine abstinence, medial prefrontal cortex, nucleus accumbens, psychostimulant use disorder, drug craving, behavioral plasticity, cognitive flexibility
- MeSH terms
- Animals, Cues, Extinction, Psychological, Glutamates, Limbic System, Male, Nerve Tissue Proteins, Substance Withdrawal Syndrome, Synapses, Granulocyte Colony-Stimulating Factor, Rats, Sprague-Dawley, Prefrontal Cortex, Cocaine-Related Disorders, Proteomics, Rats, Drug-Seeking Behavior, Craving
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