Abstract
Group II metabotropic glutamate (mGlu) receptor antagonists exerted antidepressant effects in several animal models of depression including those refractory to currently prescribed antidepressants. Moreover, group II mGlu receptor antagonists exhibited rapid and sustained antidepressant effects in animal models, as observed in ketamine treatment. AMPA receptor stimulation and subsequent activation of BDNF-TrkB and mTOR signaling mediate antidepressant effects of group II mGlu receptor antagonists. In addition, group II mGlu receptor antagonists activate serotonin neurons in the dorsal raphe nucleus by stimulation of AMPA receptor in the medial prefrontal cortex to exert antidepressant effects. These molecular and neural mechanisms were shared by ketamine. Therefore, group II mGlu receptor antagonists may show rapid and sustained antidepressant effects for patients with treatment resistant depression.
