The Toll-like receptor 4 antagonist TAK-242 induces antidepressant-like effects in a rat learned helplessness model of depression through BDNF-TrkB signaling and AMPA receptor activation.

Finding from animal models of depression indicated that Toll-like receptor 4 (TLR4) is associated with the pathophysiology of depression. Herein, the TLR4 antagonists TAK-242 and baicalin induced antidepressant-like effects in a rat learned helplessness model of depression. The antidepressant-like effects of both TLR4 antagonists were blocked by the TrkB inhibitor ANA-12. Also, the antidepressant-like effects of TAK-242 were blocked by the treatment with AMPA receptor antagonist NBQX. The antidepressant-like effects of the TLR4 antagonist TAK-242 involves BDNF-TrkB signaling and AMPA receptor activation.