PT  - JOURNAL ARTICLE
AU  - Rebecca S. Hofford
AU  - Tanner J. Euston
AU  - Rashaun S. Wilson
AU  - Katherine R. Meckel
AU  - Emily G. Peck
AU  - Arthur Godino
AU  - Joseph A. Landry
AU  - Erin S. Calipari
AU  - TuKiet T. Lam
AU  - Drew D. Kiraly
TI  - Granulocyte-Colony Stimulating Factor reduces cocaine-seeking and downregulates glutamatergic synaptic proteins in medial prefrontal cortex
AID  - 10.1101/2020.02.17.949990
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.17.949990
4099  - http://biorxiv.org/content/early/2020/02/18/2020.02.17.949990.short
4100  - http://biorxiv.org/content/early/2020/02/18/2020.02.17.949990.full
AB  - 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.