). In contrast, Conti et al (2002) showed that the absence of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) blocks antidepressant-induced increases in BDNF levels in hippocampus but does not block antidepressant responses in the FST. These paradoxical findings, however, can be reconciled in a model in which antidepressant efficacy requires a certain level of baseline BDNF (i.e., BDNF action is permissive), whereas large increases in BDNF is not essential for antidepressant efficacy (i.e., BDNF action is instructive)