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Granulocyte-colony stimulating factor controls neural and behavioral plasticity in response to cocaine
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Granulocyte-colony stimulating factor controls neural and behavioral plasticity in response to cocaine
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Journal Article
Granulocyte-colony stimulating factor controls neural and behavioral plasticity in response to cocaine
2018
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Animals
/ Behavior, Addictive - drug therapy
/ Behavior, Addictive - physiopathology
/ Behavior, Animal - drug effects
/ Brain
/ Cocaine
/ Cocaine - administration & dosage
/ Cocaine-Related Disorders - drug therapy
/ Cocaine-Related Disorders - physiopathology
/ Colonies
/ Granulocyte colony-stimulating factor
/ Granulocyte Colony-Stimulating Factor - administration & dosage
/ Granulocyte Colony-Stimulating Factor - drug effects
/ Granulocyte Colony-Stimulating Factor - metabolism
/ Humanities and Social Sciences
/ Male
/ Mice
/ Neuronal Plasticity - drug effects
/ Nucleus Accumbens - drug effects
/ Nucleus Accumbens - metabolism
/ Rats
/ Science
