Corticotropin-releasing factor-related peptides, serotonergic systems, and emotional behavior.

Corticotropin- releasing factor( CRF) is a 41-amino acid neuropeptide that is involved in stress-related physiology and behavior, including control of the hypothalamic-pituitary-adrenal (HPA) axis. Members of the CRFfamily of neuropeptides, including urocortin1 (Ucn 1), Ucn 2, and Ucn 3, bind to the G protein-coupled receptors, CRFtype 1 (CRF1) and CRF2 receptors. In addition, CRFbinding protein (CRFBP) binds both CRFand Ucn 1 and can modulate their activities. There are multiple mechanisms through which CRF-related peptides may influence emotional behavior, one of which is through altering the activity of brainstem neuromodulatory systems, including serotonergicsystems. Corticotropin- releasing factorand CRF-related peptides act within the dorsal raphe nucleus(DR), the major source for serotonin (5-HT) in the brain, to alter the neuronal activity of specific subsets of serotonergicneurons and to influence stress-related behavior. CRF-containing axonal fibers innervate the DR in a topographically organized manner, which may contribute to the ability of CRFto alter the activity of specific subsets of serotonergicneurons. CRFand CRF-related peptides can either increase or decrease serotonergicneuronal firing rates and serotonin release, depending on their concentrations and on the specific CRFreceptor subtype(s) involved. This review aims to describe the interactions between CRF-related peptides and serotonergicsystems, the consequences for stress-related behavior, and implications for vulnerability to anxiety and affective disorders.