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

Nat Commun. 2018 Jan 16;9(1):9. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Addictive / drug therapy
  • Behavior, Addictive / physiopathology
  • Behavior, Animal / drug effects*
  • Cocaine / administration & dosage
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / drug therapy*
  • Cocaine-Related Disorders / physiopathology
  • Conditioning, Operant
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Granulocyte Colony-Stimulating Factor / drug effects
  • Granulocyte Colony-Stimulating Factor / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity / drug effects*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation


  • Granulocyte Colony-Stimulating Factor
  • Cocaine