Abstract：
Major depressive disorder is one of the most prevalent mental health disorders, posing a global socioeconomic burden. Conventional antidepressant treatments have a slow onset of action, and 30% of patients show no clinically significant treatment response. The recently approved fast-acting antidepressant S-ketamine, an N-methyl-D-aspartate receptor antagonist, provides a new approach for treatment-resistant patients. However, knowledge of S-ketamine\'s mechanism of action is still being established. Depressed human subjects have lower striatal dopamine transporter (DAT) availability compared to healthy controls. Rodent studies report increased striatal dopamine concentration in response to acute ketamine administration. In vivo [18F]FE-PE2I ([18F]-(E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β-(4\'-methyl-phenyl) nortropane) positron emission tomography (PET) imaging of the DAT has not previously been applied to assess the effect of acute subanesthetic S-ketamine administration on DAT availability. We applied translational in vivo [18F]FE-PE2I PET imaging of the DAT in healthy female rats to evaluate whether an acute subanesthetic intraperitoneal dose of 15 mg/kg S-ketamine alters DAT availability. We also performed [3H]GBR-12935 autoradiography on postmortem brain sections. We found no effect of acute S-ketamine administration on striatal DAT binding using [18F]FE-PE2I PET or [3H]GBR-12935 autoradiography. This negative result does not support the hypothesis that DAT changes are associated with S-ketamine\'s rapid antidepressant effects, but additional studies are warranted.
摘要：
重度抑郁障碍是最常见的心理健康障碍之一,构成全球社会经济负担。传统的抗抑郁治疗起效缓慢，和30％的患者显示没有临床显着治疗反应。最近批准的速效抗抑郁药S-氯胺酮，一种N-甲基-D-天冬氨酸受体拮抗剂,为耐药患者提供了一种新的治疗方法。然而,关于S-氯胺酮作用机制的知识仍在建立中。与健康对照相比,抑郁的人受试者具有较低的纹状体多巴胺转运蛋白(DAT)可用性。啮齿动物研究报告了响应于急性氯胺酮给药的纹状体多巴胺浓度增加。DAT的体内[18F]FE-PE2I（[18F]-（E）-N-（3-碘丙-2-烯基）-2β-碳氟乙氧基-3β-（4'-甲基-苯基）去甲托烷）正电子发射断层扫描（PET）成像以前尚未用于评估急性亚麻醉药S-氯胺酮给药对DAT可用性的影响。我们在健康雌性大鼠中应用了DAT的体内[18F]FE-PE2IPET成像，以评估15mg/kgS-氯胺酮的急性亚麻醉药腹膜内剂量是否会改变DAT的可用性。我们还对死后脑切片进行了[3H]GBR-12935放射自显影。使用[18F]FE-PE2IPET或[3H]GBR-12935放射自显影，我们发现急性S-氯胺酮对纹状体DAT结合没有影响。这一阴性结果不支持DAT变化与S-氯胺酮的快速抗抑郁作用相关的假设。但需要更多的研究.
