Sleep Disturbance Alters Cocaine-Induced Locomotor Activity: Involvement of Striatal Neuroimmune and Dopamine Signaling.
Sleep Disturbance Alters Cocaine-Induced Locomotor Activity: Involvement of Striatal Neuroimmune and Dopamine Signaling.
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睡眠障碍改变可卡因诱导的运动活动：纹状体神经免疫和多巴胺信号的参与。
DOI：
10.3390/biomedicines10051161
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发表时间：
2022-05-18
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
睡眠障碍与药物成瘾具有高度的共病性，是药物成瘾的主要危险因素。最近的研究表明，睡眠障碍（SD）和滥用药物都可以激活小胶质细胞，而神经炎症的增加在这两种疾病的发病机制中起着至关重要的作用。小胶质细胞是否参与慢性SD对药物成瘾的贡献从未被探索过。在这项研究中，我们采用了可卡因治疗的睡眠片段（SF）小鼠模型，并检查了它们的运动活动，以及纹状体中的神经炎症水平和多巴胺信号传导，以评估它们的相互作用。我们还包括了经历可卡因戒断和激发的有或没有SF的小鼠。我们的研究结果表明，SF显着钝化可卡因诱导的运动刺激，而对小鼠的运动活动与盐水注射有边际影响。同时，SF调制可卡因对纹状体和离体分离的小胶质细胞中的神经免疫信号传导的影响。我们没有观察到治疗组之间纹状体多巴胺信号的差异。在接触可卡因和后来戒断的小鼠中，SF降低了运动敏感性，并调节了纹状体中的神经免疫和多巴胺信号。综上所述，我们的研究结果表明，SF能够通过调节神经免疫和多巴胺信号来减弱可卡因诱导的精神活性作用。我们假设SF可以影响大脑奖赏回路中的神经免疫和多巴胺信号，这可能介导睡眠障碍和药物成瘾之间的联系。
Sleep disorders have high comorbidity with drug addiction and function as major risk factors for developing drug addiction. Recent studies have indicated that both sleep disturbance (SD) and abused drugs could activate microglia, and that increased neuroinflammation plays a critical role in the pathogenesis of both diseases. Whether microglia are involved in the contribution of chronic SDs to drug addiction has never been explored. In this study, we employed a mouse model of sleep fragmentation (SF) with cocaine treatment and examined their locomotor activities, as well as neuroinflammation levels and dopamine signaling in the striatum, to assess their interaction. We also included mice with, or without, SF that underwent cocaine withdrawal and challenge. Our results showed that SF significantly blunted cocaine-induced locomotor stimulation while having marginal effects on locomotor activity of mice with saline injections. Meanwhile, SF modulated the effects of cocaine on neuroimmune signaling in the striatum and in ex vivo isolated microglia. We did not observe differences in dopamine signaling in the striatum among treatment groups. In mice exposed to cocaine and later withdrawal, SF reduced locomotor sensitivity and also modulated neuroimmune and dopamine signaling in the striatum. Taken together, our results suggested that SF was capable of blunting cocaine-induced psychoactive effects through modulating neuroimmune and dopamine signaling. We hypothesize that SF could affect neuroimmune and dopamine signaling in the brain reward circuitry, which might mediate the linkage between sleep disorders and drug addiction.
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影响因子：
4.2
作者：
Bachtell RK;Jones JD;Heinzerling KG;Beardsley PM;Comer SD
通讯作者：
Comer SD
影响因子：
3.1
作者：
DePoy LM;McClung CA;Logan RW
通讯作者：
Logan RW
影响因子：
3.4
作者：
Belin, D.;Deroche-Gamonet, V.;Jaber, M.
通讯作者：
Jaber, M.
DOI：
10.1073/pnas.0504438102
发表时间：
2005-08-09
影响因子：
11.1
作者：
Ahmed, SH;Lutjens, R;Sanna, PP
通讯作者：
Sanna, PP
影响因子：
3.6
作者：
Berro, L. F.;Hollais, A. W.;Frussa-Filho, R.
通讯作者：
Frussa-Filho, R.