In order to develop antidepressant drugs from HMF based on the “BDNF hypothesis of depression”, we need to investigate (1) whether orally (p.o.) administered HMF enters the brain; (2) whether HMF induces BDNF expression in a more physiological mouse model of depression than CORT-treated mice; and (3) the mechanisms of action of HMF. This evidence concerns the gene BDNF and major depressive disorder.