A variety of basic science, animal studies, and human studies support the idea that the neuropeptide oxytocin may be effective against anxiety in humans. For example, plasma oxytocin levels may function as an index of central serotonin (5-HT) function in human subjects, and serotonin is well-known to be involved in clinical anxiety disorders. Since oxytocin is released directly from limbic-hypothalamic cells, this response presumably represents a direct central assessment of 5-HT response in limbic-hypothalamus (Lee 2003). In animal models, Ring 2006 examined the effects of oxytocin on both behavioral and autonomic parameters of the anxiety response in male mice using three pharmacologically validated preclinical models of anxiety: the four-plate test (FPT), elevated zero maze (EZM), and stress-induced hyperthermia (SIH). The results from this study provide specific behavioral and autonomic evidence of anxiolytic-like effects for oxytocin. In primates, Emiliano et al 2007 found support for the idea that that SSRIs' therapeutic effects on social affiliation and anxiety may be mediated in part through components of the oxytocin system. Human studies include Kosfeld et al (2005), who demonstrated that oxytocin administered intranasally to healthy human subjects in a double-blind, placebo controlled study increased levels of trust. As well, Kirsch et al (2005) showed that intranasal oxytocin reduced activation of brain circuits involved in fear in human subjects. Finally, Scantamburlo (2007) showed a significant negative correlation between oxytocin and the scored symptoms depression and anxiety. These studies clearly suggest the potential utility of OTR agonism as a therapeutically relevant mechanism of action for novel anxiolytics in both sexes.