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

• Published in: Nature communications Vol. 9; no. 1; pp. 9 - 14
• Main Authors: Calipari, Erin S., Godino, Arthur, Peck, Emily G., Salery, Marine, Mervosh, Nicholas L., Landry, Joseph A., Russo, Scott J., Hurd, Yasmin L., Nestler, Eric J., Kiraly, Drew D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16-01-2018; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/1689/5; 631/378/371; Adaptation; Addictions; Addictive behaviors; Animal behavior; Animals; Behavior, Addictive - drug therapy; Behavior, Addictive - physiopathology; Behavior, Animal - drug effects; Behavioral plasticity; Brain; Cerebrospinal fluid; Cocaine; Cocaine - administration & dosage; Cocaine - pharmacology; Cocaine-Related Disorders - drug therapy; Cocaine-Related Disorders - physiopathology; Colonies; Colony-stimulating factor; Conditioning, Operant; Drug abuse; Drug therapy; Granulocyte colony-stimulating factor; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - drug effects; Granulocyte Colony-Stimulating Factor - metabolism; Granulocytes; Humanities and Social Sciences; Leukocytes (granulocytic); Male; Mice; Mice, Inbred C57BL; Motivation; multidisciplinary; Narcotics; Neural plasticity; Neuronal Plasticity - drug effects; Nucleus accumbens; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Pharmacology; Prefrontal cortex; Rats; Rats, Sprague-Dawley; Reinforcement; Science; Science (multidisciplinary); Up-Regulation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-01881-x

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.
Cocaine addiction is accompanied by dysfunction in neural circuits related to reward, but it is unclear how these adaptations occur. Here, authors identify granulocyte-colony stimulating factor as a potent mediator of cocaine-induced adaptations, and show that it can alter the motivation for cocaine.