Department of Toxicology, Jagiellonian University, Collegium Medicum, Medyczna 9, PL 30-688 Kraków, Poland.
Pharmacol Rep. 2010 Nov-Dec;62(6):1186-90. doi: 10.1016/s1734-1140(10)70381-9.
Several lines of evidence suggest an antidepressant-like activity for 3-[(methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP), a highly selective, non-competitive antagonist of metabotropic glutamate receptors subtype 5 (mGluR(5)). This effect has been observed following both acute and chronic MTEP treatments in behavioral tests and experimental models of depression, such as the forced swim test (FST), the tail suspension test, and the olfactory bulbectomy model of depression. However, the mechanism of action for mGluR(5) antagonists remains unclear. The aim of this study was to investigate whether the antidepressant-like action of MTEPis dependent on ionotropic glutamatergic receptors. Male Albino Swiss mice were used, and antidepressant-like activity was evaluated using the FST. The antidepressant-like effect of MTEP (0.3 mg/kg) was significantly antagonized by pre-treatment with the NMDA receptor agonist N-methyl-D-aspartic acid (NMDA, 75 mg/kg, i.p.). The AMPA receptor antagonist NBQX (10 mg/kg, i.p.) did not affect the MTEP activity. Our results indicate that the antidepressant-like activity of MTEP in the FST involves NMDA but not AMPA receptors and suggest that the interaction between mGluR(5) and NMDA receptors plays an important role in the underlying antidepressant mechanism(s).
有几条证据表明，3-[(甲基-1,3-噻唑-4-基)乙炔基]吡啶（MTEP）具有抗抑郁样活性，MTEP 是代谢型谷氨酸受体亚型 5（mGluR(5)）的高度选择性、非竞争性拮抗剂。这种效应在行为测试和抑郁症的实验模型中，如强迫游泳试验（FST）、悬尾试验和抑郁症嗅球切除术模型中，无论是在急性还是慢性 MTEP 治疗后都观察到了。然而，mGluR(5)拮抗剂的作用机制仍不清楚。本研究旨在探讨 MTEP 的抗抑郁样作用是否依赖于离子型谷氨酸能受体。使用雄性白化瑞士小鼠，通过 FST 评估抗抑郁样活性。MTEP（0.3mg/kg）的抗抑郁样作用被 NMDA 受体激动剂 N-甲基-D-天冬氨酸（NMDA，75mg/kg，腹腔注射）预处理显著拮抗。AMPA 受体拮抗剂 NBQX（10mg/kg，腹腔注射）不影响 MTEP 活性。我们的结果表明，MTEP 在 FST 中的抗抑郁样活性涉及 NMDA 但不涉及 AMPA 受体，表明 mGluR(5)和 NMDA 受体之间的相互作用在潜在的抗抑郁机制中起着重要作用。
