Neuropharmacological study on drug development targeting forbrain metabotropic glutamate 2/3 receptors

只有30-50%的抑郁症患者在抗抑郁药物治疗后进入缓解期。因此，发现新的抑郁症病理生理的神经元机制以及更有效的治疗是必要的。在本研究中，代谢性谷氨酸2/3受体拮抗剂在慢性糖皮质激素治疗小鼠（常规抗抑郁性抑郁症动物模型）中显示出抗抑郁样作用。慢性糖皮质激素治疗显著增加前额叶多巴胺能活性，这种增强的活性可被代谢性谷氨酸2/3受体拮抗剂阻断，但常规抗抑郁药不能。目前的研究结果表明，代谢性谷氨酸2/3受体是治疗难治性抑郁症患者的一个有希望的靶点。

Only 30-50% of patients with depression enter remission after antidepressant treatment. Thus, discovering novel neuronal mechanisms of pathophysiology of depression as well as more effective treatments are necessary. In this study, metabotropic glutamate 2/3 receptor antagonists showed antidepressant-like effects in chronic glucocorticoid-treated mice, an animal model of conventional antidepressant-resistant depression. Chronic glucocorticoid treatment markedly increased prefrontal dopaminergic activity, and this enhanced activity was blocked by metabotropic glutamate 2/3 receptor antagonists, but not conventional antidepressants. The present findings suggest that the metabotropic glutamate 2/3 receptor is a promising target for the treatment of patients with treatment-resistant depression.