Corticotropin-releasing factor-related peptides, serotonergic systems, and emotional behavior.
2013
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.
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