In addition, this study provides evidence showing that among the multiple mechanisms involved in the development of depression-like neurobehavior, the inhibition of the CREB pathway, including downregulation of ERK phosphorylation, PKA activity, CREB phosphorylation, and CREB DNA-binding activity, might contribute in part to the decreased expression of BDNF and the resulting depression-like phenotypes. The gene discussed is CREB1; the disease is major depressive disorder.