Kosten Lauren, Verhaeghe Jeroen, Wyffels Leonie, Stroobants Sigrid, Staelens Steven
1 Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.
2 Department of Nuclear Medicine, University Hospital Antwerp, Antwerp, Belgium.
Mol Imaging. 2018 Jan-Dec;17:1536012118788636. doi: 10.1177/1536012118788636.
Detecting changes in metabotropic glutamate receptor 5 (mGluR5) availability through molecular imaging with the positron emission tomography (PET) tracer [C]ABP688 is valuable for studying dysfunctional glutamate transmission associated with neuropsychiatric disorders. Using an infusion protocol in rats, we visualized the acute effect of subanesthetic doses of ketamine on mGluR5 in rat brain. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist known to increase glutamate release. Imaging was performed with a high-affinity PET ligand [C]ABP688, a negative allosteric modulator of mGluR5. Binding did not change significantly from baseline to ketamine in any region, thereby confirming previous literature with other NMDA receptor antagonists in rodents. Hence, in rats, we could not reproduce the findings in a human setup showing significant decreases in the [C]ABP688 binding after a ketamine bolus followed by ketamine infusion. Species differences may have contributed to the different findings in the present study of rats. In conclusion, we could not confirm in rats that endogenous glutamate increases by ketamine infusion are reflected in [C]ABP688 binding decreases as was previously shown for humans.
通过正电子发射断层扫描（PET）示踪剂[C]ABP688进行分子成像来检测代谢型谷氨酸受体5（mGluR5）可用性的变化，对于研究与神经精神疾病相关的谷氨酸传递功能障碍具有重要价值。我们采用大鼠输注方案，观察了亚麻醉剂量氯胺酮对大鼠脑内mGluR5的急性影响。氯胺酮是一种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，已知可增加谷氨酸释放。使用高亲和力PET配体[C]ABP688（一种mGluR5的负变构调节剂）进行成像。在任何区域，从基线到氯胺酮处理后，结合均无显著变化，从而证实了先前在啮齿动物中使用其他NMDA受体拮抗剂的文献报道。因此，在大鼠中，我们无法重现人体研究中的结果，即在静脉注射氯胺酮后再进行氯胺酮输注，[C]ABP688结合显著降低。物种差异可能导致了本研究中大鼠出现不同的结果。总之，我们无法在大鼠中证实，如先前在人体中所显示的那样，氯胺酮输注导致内源性谷氨酸增加会反映在[C]ABP688结合降低上。
