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Nat Commun. 2018 Jan 16;9(1):9. doi: 10.1038/s41467-017-01881-x.

Granulocyte-colony stimulating factor controls neural and behavioral plasticity in response to cocaine.

Author information

1
Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
2
Department of Pharmacology, Vanderbilt Center for Addiction Research, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
3
Department of Biology, École Normale Supérieure de Lyon, Lyon, France.
4
Department of Psychiatry, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
5
Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. drew.kiraly@mssm.edu.
6
Department of Psychiatry, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. drew.kiraly@mssm.edu.
7
Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA. drew.kiraly@mssm.edu.

Abstract

Cocaine addiction is characterized by dysfunction in reward-related brain circuits, leading to maladaptive motivation to seek and take the drug. There are currently no clinically available pharmacotherapies to treat cocaine addiction. Through a broad screen of innate immune mediators, we identify granulocyte-colony stimulating factor (G-CSF) as a potent mediator of cocaine-induced adaptations. Here we report that G-CSF potentiates cocaine-induced increases in neural activity in the nucleus accumbens (NAc) and prefrontal cortex. In addition, G-CSF injections potentiate cocaine place preference and enhance motivation to self-administer cocaine, while not affecting responses to natural rewards. Infusion of G-CSF neutralizing antibody into NAc blocks the ability of G-CSF to modulate cocaine's behavioral effects, providing a direct link between central G-CSF action in NAc and cocaine reward. These results demonstrate that manipulating G-CSF is sufficient to alter the motivation for cocaine, but not natural rewards, providing a pharmacotherapeutic avenue to manipulate addictive behaviors without abuse potential.

PMID:
29339724
PMCID:
PMC5770429
DOI:
10.1038/s41467-017-01881-x
[Indexed for MEDLINE]
Free PMC Article

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