Granulocyte colony-stimulating factor (G-CSF) enhances cocaine effects in the nucleus accumbens via a dopamine release-based mechanism.
Granulocyte colony-stimulating factor (G-CSF) enhances cocaine effects in the nucleus accumbens via a dopamine release-based mechanism.
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DOI：
10.1007/s00213-021-05967-9
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发表时间：
2021-12
影响因子：
3.4
通讯作者：
Calipari, Erin S.
中科院分区：
文献类型：
--
作者：
Brady, Lillian J.;Erickson, Kirsty R.;Lucerne, Kelsey E.;Osman, Aya;Kiraly, Drew D.;Calipari, Erin S.
可卡因使用障碍与免疫功能的改变有关，包括人类多种外周细胞因子表达的改变-其中几种与药物使用有关。患有可卡因使用障碍的个体显示出对药物相关线索的免疫系统反应的改变，突出了大脑和免疫系统之间的相互作用是可卡因使用障碍的发展和表达的关键因素。我们先前已经在动物模型中证明，可卡因使用上调血清和髓核（NAc）中粒细胞集落刺激因子（G-CSF）（一种多效性细胞因子）的表达。G-CSF信号转导与可卡因在多个行为领域的行为反应有因果关系。本研究的目的是确定G-CSF的增加是否改变可卡因对多巴胺系统的药效学作用，以及这是否通过局部NAc微回路内的直接机制发生。我们发现，全身性G-CSF注射增加可卡因对多巴胺末梢的影响。在可卡因存在下，多巴胺水平的增强是通过基于释放的机制发生的，而不是通过对多巴胺转运蛋白的影响-因为在G-CSF治疗后摄取率没有变化。重要的是，这种效应可以通过将G-CSF急性浴应用于多巴胺末梢来重现，这种效应被先前的G-CSF治疗所阻断，表明直接和全身暴露的机制基础相似。这项工作强调了免疫系统和精神兴奋剂效应之间的关键相互作用，这种相互作用可以改变药物反应，并可能在可卡因使用障碍的脆弱性中发挥作用。
Cocaine use disorder is associated with alterations in immune function including altered expression of multiple peripheral cytokines in humans - several of which correlate with drug use. Individuals suffering from cocaine use disorder show altered immune system responses to drug-associated cues, highlighting the interaction between the brain and immune system as a critical factor in the development and expression of cocaine use disorder. We have previously demonstrated in animal models that cocaine use upregulates expression of granulocyte colony stimulating factor (G-CSF) - a pleiotropic cytokine - in the serum and the nucleus accumbens (NAc). G-CSF signaling has been causally linked to behavioral responses to cocaine across multiple behavioral domains. The goal of this study was to define whether increases in G-CSF alter the pharmacodynamic effects of cocaine on the dopamine system and whether this occurs via direct mechanisms within local NAc microcircuits. We find that systemic G-CSF injection increases cocaine effects on dopamine terminals. The enhanced dopamine levels in the presence of cocaine occur through a release-based mechanism, rather than through effects on the dopamine transporter - as uptake rates were unchanged following G-CSF treatment. Critically, this effect could be recapitulated by acute bath application of G-CSF to dopamine terminals, an effect that was occluded by prior G-CSF treatment, suggesting a similar mechanistic basis for direct and systemic exposures. This work highlights the critical interaction between the immune system and psychostimulant effects that can alter drug responses and may play a role in vulnerability to cocaine use disorder.
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影响因子：
7.4
作者：
Felger JC;Miller AH
通讯作者：
Miller AH
影响因子：
1.7
作者：
Fox, Helen C.;D'Sa, Carrol;Kimmerling, Anne;Siedlarz, Kristen M.;Tuit, Keri L.;Stowe, Raymond;Sinha, Rajita
通讯作者：
Sinha, Rajita
影响因子：
4.2
作者：
Huang, Hsin-Yi;Lin, Shinn-Zong;Wang, Mei-Jen
通讯作者：
Wang, Mei-Jen
影响因子：
5.9
作者：
López AJ;Johnson AR;Euston TJ;Wilson R;Nolan SO;Brady LJ;Thibeault KC;Kelly SJ;Kondev V;Melugin P;Kutlu MG;Chuang E;Lam TT;Kiraly DD;Calipari ES
通讯作者：
Calipari ES
影响因子：
56.9
作者：
Beattie, EC;Stellwagen, D;Malenka, RC
通讯作者：
Malenka, RC