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首页> 外文期刊>CNS neuroscience & therapeutics. >Aquaporin‐4 Deficiency Attenuates Opioid Dependence through Suppressing Glutamate Transporter‐1 Down‐regulation and Maintaining Glutamate Homeostasis
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Aquaporin‐4 Deficiency Attenuates Opioid Dependence through Suppressing Glutamate Transporter‐1 Down‐regulation and Maintaining Glutamate Homeostasis

机译：Aquaporin-4缺乏症通过抑制谷氨酸转运蛋白-1下调并维持谷氨酸稳态来减轻阿片类药物的依赖性。

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Summary Background Glutamate homeostasis plays a critical role in mediating the addiction‐related behaviors. Therefore, preventing the disruption or reestablishing of it is a novel strategy for the treatment of addiction. Glutamate transporters are responsible for clearing extracellular glutamate and maintaining glutamate homeostasis. Our previous work demonstrated that aquaporin‐4 ( AQP 4) deficiency attenuated morphine dependence, but the mechanisms are unclear. According to the recent evidence that AQP 4 might form a functional complex with glutamate transporter‐1 ( GLT ‐1), this study focused on whether AQP 4 participates in the modulation of GLT ‐1 and glutamate homeostasis in morphine‐dependent mice. Results We found that AQP 4 knockout prevented the down‐regulations of GLT ‐1 expression and glutamate clearance when mice were repeatedly treated with morphine. Further study revealed that inhibition of GLT ‐1 by dihydrokainic acid ( DHK ) initiated morphine dependence in AQP 4 knockout mice. In addition, AQP 4 knockout abolished both decreases and increases in the extracellular glutamate levels in the prefrontal cortex during repeated morphine treatment and naloxone‐precipitated withdrawal. Conclusion AQP 4 deficiency suppresses the down‐regulation of GLT ‐1, and the disruption of glutamate homeostasis caused by repeated exposure to morphine, pointing to a strategy for maintaining glutamate homeostasis and thereby treating addiction through the modulation of AQP 4 function and expression.
机译：发明背景谷氨酸稳态在介导成瘾相关行为中起着至关重要的作用。因此，防止其破坏或重建是治疗成瘾的新策略。谷氨酸转运蛋白负责清除细胞外谷氨酸并维持谷氨酸稳态。我们以前的工作表明，水通道蛋白4（AQP 4）缺乏症减弱了吗啡依赖性，但机制尚不清楚。根据最近的证据表明AQP 4可能与谷氨酸转运蛋白1（GLT -1）形成功能复合物，本研究着重于AQP 4是否参与吗啡依赖性小鼠的GLT -1和谷氨酸稳态的调节。结果我们发现，当反复用吗啡治疗小鼠时，AQP 4基因敲除可防止GLT -1表达下调和谷氨酸清除率降低。进一步的研究表明，二氢海藻酸（DHK）对GLT -1的抑制作用会在AQP 4基因敲除小鼠中引发吗啡依赖性。此外，在反复吗啡治疗和纳洛酮沉淀戒断过程中，AQP 4敲除消除了额叶前额叶皮质细胞外谷氨酸水平的降低和升高。结论AQP 4缺乏会抑制GLT -1的下调，以及反复接触吗啡引起的谷氨酸稳态的破坏，这表明了维持谷氨酸稳态的策略，从而通过调节AQP 4的功能和表达来治疗成瘾。

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