Anxiolytic-like effects of translocator protein (TSPO) ligand ZBD-2 in an animal model of chronic pain.
Anxiolytic-like effects of translocator protein (TSPO) ligand ZBD-2 in an animal model of chronic pain.
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易位蛋白 (TSPO) 配体 ZBD-2 在慢性疼痛动物模型中的抗焦虑样作用。
DOI：
10.1186/s12990-015-0013-6
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发表时间：
2015-03-26
期刊：
影响因子：
3.3
通讯作者：
Zhao MG
中科院分区：
文献类型：
--
作者：
Wang DS;Tian Z;Guo YY;Guo HL;Kang WB;Li S;Den YT;Li XB;Feng B;Feng D;Zhao JN;Liu G;Zhao MG
转运蛋白（18kda） （TSPO）的激活已被证明在应激反应和应激相关疾病中介导快速抗焦虑作用。该蛋白参与内源性神经类固醇的合成，促进γ-氨基丁酸（GABA）介导的中枢神经系统神经传递。然而，对于TSPO在慢性疼痛诱导的焦虑样行为中的功能和潜在机制知之甚少。本研究采用了新型TSPO配体n-苄基- n-乙基-2-（7,8-二氢-7-苄基-8-氧-2-苯基- 9h -嘌呤-9-基）乙酰胺（ZBD-2）。我们发现zdb -2（0.15或1.5 mg/kg）可显著减轻后爪注射完全弗氏佐剂（CFA）引起的慢性炎症性疼痛小鼠的焦虑样行为。然而，治疗并没有改变后爪的痛觉阈值或炎症。后爪注射CFA诱导基底外侧杏仁核（BLA） TSPO、glur1 -含α-氨基-3-羟基-5-甲基-4-异唑丙酸（AMPA）受体和nr2b -含n -甲基-d-天冬氨酸（NMDA）受体上调。ZBD-2可逆转cfa注射小鼠BLA中上述蛋白的改变。电生理记录显示ZBD-2可以防止cfa注射小鼠BLA突触兴奋性和抑制性传递的不平衡。因此，作为TSPO的新型配体，ZBD-2具有抗焦虑作用，但不影响慢性疼痛小鼠的伤害知觉阈值。ZBD-2的抗焦虑作用与调节BLA中兴奋性和抑制性传递的平衡有关。
The activation of Translocator protein (18 kDa) (TSPO) has been demonstrated to mediate rapid anxiolytic efficacy in stress response and stress-related disorders. This protein is involved in the synthesis of endogenous neurosteroids that promote γ-aminobutyric acid (GABA)-mediated neurotransmission in the central neural system. However, little is known about the functions and the underlying mechanisms of TSPO in chronic pain-induced anxiety-like behaviors. The novel TSPO ligand N-benzyl-N-ethyl-2-(7,8-dihydro-7-benzyl-8-oxo-2-phenyl-9H-purin-9-yl) acetamide (ZBD-2) was used in the present study. We found that ZBD-2 (0.15 or 1.5 mg/kg) significantly attenuated anxiety-like behaviors in mice with chronic inflammatory pain induced by hindpaw injection of complete Freund’s adjuvant (CFA). However, the treatment did not alter the nociceptive threshold or inflammation in the hindpaw. Hindpaw injection of CFA induced the upregulation of TSPO, GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and NR2B-containing N-methyl-d-aspartate (NMDA) receptors in the basolateral amygdala (BLA). ZBD-2 administration reversed the alterations of the abovementioned proteins in the BLA of the CFA-injected mice. Electrophysiological recording revealed that ZBD-2 could prevent an imbalance between excitatory and inhibitory transmissions in the BLA synapses of CFA-injected mice. Therefore, as the novel ligand of TSPO, ZBD-2 induced anxiolytic effects, but did not affect the nociceptive threshold of mice under chronic pain. The anxiolytic effects of ZBD-2 were related to the regulation of the balance between excitatory and inhibitory transmissions in the BLA.
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