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选择性 A1 和 A2A 腺苷受体拮抗剂与镁和锌离子在小鼠中的相互作用:行为、生化和分子研究。

The Interaction of Selective A1 and A2A Adenosine Receptor Antagonists with Magnesium and Zinc Ions in Mice: Behavioural, Biochemical and Molecular Studies.

机构信息

Chair and Department of Applied and Social Pharmacy, Laboratory of Preclinical Testing, Medical University of Lublin, 1 Chodźki Street, PL 20-093 Lublin, Poland.

Chair and Department of Toxicology, Medical University of Lublin, 8 Chodźki Street, PL 20-093 Lublin, Poland.

出版信息

Int J Mol Sci. 2021 Feb 12;22(4):1840. doi: 10.3390/ijms22041840.

Abstract

The purpose of the study was to investigate whether the co-administration of Mg and Zn with selective A1 and A2A receptor antagonists might be an interesting antidepressant strategy. Forced swim, tail suspension, and spontaneous locomotor motility tests in mice were performed. Further, biochemical and molecular studies were conducted. The obtained results indicate the interaction of DPCPX and istradefylline with Mg and Zn manifested in an antidepressant-like effect. The reduction of the BDNF serum level after co-administration of DPCPX and istradefylline with Mg and Zn was noted. Additionally, Mg or Zn, both alone and in combination with DPCPX or istradefylline, causes changes in expression, DPCPX or istradefylline co-administered with Zn increases expression as compared to a single-drug treatment, co-administration of tested agents does not have a more favourable effect on expression. Moreover, the changes obtained in , , expression show that DPCPX-Mg, DPCPX-Zn, istradefylline-Mg and istradefylline-Zn co-treatment may have greater antioxidant capacity benefits than administration of DPCPX and istradefylline alone. It seems plausible that a combination of selective A1 as well as an A2A receptor antagonist and magnesium or zinc may be a new antidepressant therapeutic strategy.

摘要

本研究旨在探讨 Mg 和 Zn 与选择性 A1 和 A2A 受体拮抗剂联合使用是否是一种有趣的抗抑郁策略。在小鼠中进行了强迫游泳、悬尾和自发运动活力测试。此外,还进行了生化和分子研究。研究结果表明,DPCPX 和伊曲茶碱与 Mg 和 Zn 的相互作用表现出抗抑郁样作用。联合使用 DPCPX 和伊曲茶碱与 Mg 和 Zn 后,BDNF 血清水平降低。此外,Mg 或 Zn 单独或与 DPCPX 或伊曲茶碱联合使用均会导致 表达发生变化,与单一药物治疗相比,DPCPX 或伊曲茶碱联合 Zn 会增加 表达,而联合使用测试药物对 表达没有更有利的影响。此外, 、 、 表达的变化表明,DPCPX-Mg、DPCPX-Zn、伊曲茶碱-Mg 和伊曲茶碱-Zn 联合治疗可能比单独使用 DPCPX 和伊曲茶碱具有更大的抗氧化能力益处。联合使用选择性 A1 以及 A2A 受体拮抗剂和镁或锌可能是一种新的抗抑郁治疗策略。

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