3 years ago

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

Granulocyte-colony stimulating factor controls neural and behavioral plasticity in response to cocaine
Scott J. Russo, Joseph A. Landry, Nicholas L. Mervosh, Drew D. Kiraly, Yasmin L. Hurd, Erin S. Calipari, Marine Salery, Emily G. Peck, Arthur Godino, Eric J. Nestler
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.

Publisher URL: https://www.nature.com/articles/s41467-017-01881-x

DOI: 10.1038/s41467-017-01881-x

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