Granulocyte-colony stimulating factor reduces cocaine-seeking and downregulates glutamatergic synaptic proteins in medial prefrontal cortex

Rebecca S. Hofford, Tanner J. Euston, Rashaun S. Wilson, Katherine R. Meckel, Emily G. Peck, Arthur Godino, Joseph A. Landry, Erin S. Calipari, Tukiet T. Lam, Drew D. Kiraly

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Psychostimulant use disorder is a major public health issue, and despite the scope of the problem there are currently no Food and Drug Administration (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. Male 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. 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. 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 multiregion discovery proteomics analyses, these studies identify a novel mechanism underlying G-CSF effects on behavioral plasticity.

Original languageEnglish
Pages (from-to)1553-1565
Number of pages13
JournalJournal of Neuroscience
Issue number7
StatePublished - 17 Jan 2021


  • Cocaine
  • Cytokine
  • Neuroimmune
  • Reinstatement


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