Pharmacological and transgenic studies show that brain and pituitary CRF1Rs mediate many of the functional stress-like effects of the CRF system (Heinrichs and Koob 2004). CRF and the Ucn peptides have a wide distribution throughout the brain, but there are particularly high concentrations of cell bodies in the paraventricular nucleus of the hypothalamus, the basal forebrain (notably the extended amygdala), and the brainstem (Swanson et al. 1983). Ucn1 binds with equal affinity to CRF1R and CRF2R, and Ucn2 and Ucn3 are CRF2R agonists (Hauger et al. 2006; Pioszak et al. 2008). CRF and the Ucn peptides exert their behavioral and neuroendocrine actions through central hypothalamic and extrahypothalamic pathways (Hauger et al. 2006; Heilig and Koob 2007; Heinrichs and Koob 2004; Koob and Le Moal 2008).
