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.

中文翻译：

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粒细胞集落刺激因子控制可卡因对神经和行为的可塑性。

可卡因成瘾的特征在于与奖励有关的大脑回路功能障碍，导致寻找和服用该药物的不良适应动机。目前尚无可用于治疗可卡因成瘾的临床药物疗法。通过先天免疫介体的广泛筛选，我们确定粒细胞集落刺激因子（G-CSF）是可卡因诱导的适应的有效介体。在这里，我们报告G-CSF增强可卡因诱导伏隔核（NAc）和前额叶皮层神经活动的增加。此外，G-CSF注射增强了可卡因的偏爱性，并增强了自我管理可卡因的动机，同时不影响对自然奖励的反应。将G-CSF中和抗体注入​​NAc会阻止G-CSF调节可卡因的行为影响，提供了NAc中中央G-CSF行动与可卡因奖励之间的直接联系。这些结果表明，操纵G-CSF足以改变可卡因的动机，但不能改变自然报酬，从而提供了一种药物成瘾的途径来操纵成瘾行为而无滥用潜力。