release (Jones et al., 1978). Some of these effects occur following the injection of NK1R antagonists in unstressed animals, suggesting a tonic suppression of HPA axis activity by SP/NK1R. Therefore, NK1R activation may regulate the HPA axis in a manner that depends on the state of the system tonically inhibit HPA axis activity at rest, while enhancing it during exposure to stressors. In humans, the latter effects appear to dominate, because administration of an NK1R antagonist over the course of several weeks did not influence basal cortisol levels, but did block stress-induced release of both ACTH and cortisol (George et al., 2008).
