Allopregnanolone induces antidepressant-like effects through BDNF-TrkB signaling independent from AMPA receptor activation in a rat learned helplessness model of depression

摘要

Allopregnanolone (ALLO, 3 alpha 5 alpha-tetrahydroprogesterone) was found to be effective for depressed patients. Animal models of depression indicate that ALLO is associated with the pathophysiology of depression. Traditional antidepressant drugs produce antidepressant effects via the monoamine system, with consequent upregulation of brain-derived neurotrophic factor (BDNF). This study was designed to examine whether the antidepressant effects of ALLO involve BDNF-TrkB signaling or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activation on the learned helplessness paradigm. The antidepressant-like effect of ALLO infusion into the cerebral ventricle was blocked by coinfusion of TrkB inhibitor ANA-12, but not by co-administration of AMPA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfoamoylbenzo(f)quinoxaline (NBQX). Thus, the antidepressant-like effect of ALLO involves BDNF signaling independent from AMPA receptor activation.