In this study, we examined the effects of IL-18 deficiency on behaviors and gene expression profiles in 6 brain regions. IL-18(-/-) mice reduced depressive-like behavior and changed gene expressions predominantly in the amygdala compared with wild-type mice. Pathway analysis of the differentially expressed genes ranked behavior as the top-scored biological function. Of note, the absence of IL-18 decreased Avp, Hat, Oxt, and Pmch mRNA levels and the number of arginine vasopressin- and oxytocin-positive cells in the amygdala, but not in the hypothalamus. Our results suggest that IL-18-dependent vasopressinergic and oxytocinergic circuitry in the amygdala may regulate depressive-like behaviors in mice. (C) 2010 Elsevier B.V. All rights reserved.