BDNF and major depressive disorder: Many preclinical studies have been unable to demonstrate these changes produced by stress or ATDs or have obtained opposing results [80, 81]: conditional BDNF knockout show no depressive behavior [55], BDNF exerts a powerful pro-depressant action in the ventral tegmental area (VTA) and nucleus accumbens (its expression in nucleus accumbens is increased by stress [82], direct infusion into these zones increases behaviors related to depression [35, 83] and a selective knockout without the gene encoding BDNF in this circuit has an antidepressant effect) [82].