咖啡因联合氟哌啶醇可减少帕金森病实验模型中的疲劳——一种针对 AR-DR 杂二聚体拮抗的前瞻性研究。
Caffeine plus haloperidol reduces fatigue in an experimental model of Parkinson's disease - a prospective to AR-DR heterodimer antagonism.
机构信息
Laboratory of Exercise Biology (LaBioEx), Department of Health Sciences, Federal University of Santa Catarina (UFSC), Ararangua, SC, 88905-120, Brazil.
出版信息
Purinergic Signal. 2024 Feb;20(1):29-34. doi: 10.1007/s11302-023-09933-2. Epub 2023 Mar 15.
Fatigue is a non-motor symptom of Parkinson's disease (PD). Adenosine receptor (AR) and compromised dopamine neurotransmission are linked to fatigue. Studies demonstrate that AR antagonism potentiates dopamine transmission via dopamine receptor D (DR). However, the heterodimer form of AR-DR in the striatum prompted questions about the therapeutic targets for PD patients. This study investigates the effects of caffeine (AR non-selective antagonist) plus haloperidol (DR selective antagonist) treatment in the fatigue induced by the reserpine model of PD. Reserpinized mice showed impaired motor control in the open field test (p < 0.05) and fatigue in the grip strength meter test (p < 0.05). L-DOPA and caffeine plus haloperidol similarly increased motor control (p < 0.05) and mitigated fatigue (p < 0.05). Our results support the AR-DR heterodimer participation in the central fatigue of PD, and highlight the potential of AR-DR antagonism in the management of PD.
疲劳是帕金森病（PD）的一种非运动症状。腺苷受体（AR）和多巴胺神经传递受损与疲劳有关。研究表明，AR 拮抗剂通过多巴胺受体 D（DR）增强多巴胺传递。然而，纹状体中的 AR-DR 异二聚体形式引发了关于 PD 患者治疗靶点的问题。本研究探讨了咖啡因（AR 非选择性拮抗剂）加氟哌啶醇（DR 选择性拮抗剂）治疗利血平诱导的 PD 疲劳模型的效果。利血平化小鼠在旷场试验中表现出运动控制受损（p<0.05）和握力计试验中疲劳（p<0.05）。L-多巴和咖啡因加氟哌啶醇同样增加了运动控制（p<0.05）并减轻了疲劳（p<0.05）。我们的结果支持 AR-DR 异二聚体参与 PD 的中枢疲劳，并强调了 AR-DR 拮抗在 PD 管理中的潜力。
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