Nowak Gabriel, Pomierny-Chamioło Lucyna, Siwek Agata, Niedzielska Ewa, Pomierny Bartosz, Pałucha-Poniewiera Agnieszka, Pilc Andrzej
Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
Jagiellonian University Medical College, Faculty of Pharmacy, Department of Toxicology, Medyczna 9, PL 30-688 Kraków, Poland.
Neuropharmacology. 2014 Sep;84:46-51. doi: 10.1016/j.neuropharm.2014.04.016. Epub 2014 May 4.
Metabotropic glutamate 5 (mGlu5) receptors are functionally connected with NMDA receptors. The antidepressant activity of the NMDA receptor antagonist ketamine in both preclinical and clinical studies, along with the antidepressant-like activities of negative allosteric modulators (NAMs) of mGlu5, led us to investigate if prolonged administration of various antidepressant drugs or the mGlu5 NAM, MTEP, causes changes in mGlu5 receptor availability or protein expression or in expression of Homer proteins in the rat brain. Our results clearly show that prolonged treatment with antidepressants with various mechanisms of action (such as escitalopram, reboxetine, milnacipran, moclobemide and imipramine) or with MTEP led to significant increases in [(3)H]MPEP binding in homogenates of the hippocampus and/or cerebral cortex. Increases in mGlu5 expression were also observed, though they did not always parallel the increase in binding. The results indicate that adaptive up-regulation of mGlu5 receptors may be a common change induced by antidepressant drugs.
代谢型谷氨酸受体5（mGlu5）与N-甲基-D-天冬氨酸（NMDA）受体存在功能联系。在临床前和临床研究中，NMDA受体拮抗剂氯胺酮的抗抑郁活性，以及mGlu5负变构调节剂（NAMs）的类抗抑郁活性，促使我们研究长期给予各种抗抑郁药物或mGlu5 NAM（MTEP）是否会导致大鼠脑内mGlu5受体可用性、蛋白表达或Homer蛋白表达发生变化。我们的结果清楚地表明，长期用具有不同作用机制的抗抑郁药（如艾司西酞普兰、瑞波西汀、米那普明、吗氯贝胺和丙咪嗪）或MTEP进行治疗，会导致海马体和/或大脑皮层匀浆中[³H]MPEP结合显著增加。还观察到mGlu5表达增加，尽管其增加并不总是与结合增加平行。结果表明，mGlu受体5的适应性上调可能是抗抑郁药物诱导的常见变化。
