Granulocyte-colony stimulating factor controls neural and behavioral plasticity in response to cocaine.
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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. |
Year of Publication | :
2018
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Journal | :
Nature communications
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Volume | :
9
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Issue | :
1
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Number of Pages | :
9
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Date Published | :
2018
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URL | :
http://dx.doi.org/10.1038/s41467-017-01881-x
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DOI | :
10.1038/s41467-017-01881-x
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Short Title | :
Nat Commun
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