Peptides that fine-tune the serotonin system.
The dorsal raphe nucleus (DR) contains serotonin (5-HT) neurons that innervate the cortex and limbic system and through these projections is thought to regulate cognition and behavior. Clinical and pharmacological findings implicate dysfunctions in the DR-5-HT system in affective disorders, including anxiety, depression and suicide. Although the DR is often considered in light of its 5-HT neurons, recent studies underscore the complexity of this nucleus and its heterogeneous nature. Of particular interest, are peptides that are either present within neurons in the DR, innervate DR-5-HT neurons or act upon local circuitry within the DR to indirectly impact on this 5-HT system. These peptides are positioned to fine-tune the activity of selective groups of serotonergic neurons within the DR and thereby 5-HT release in different terminal fields. This review will focus on substance P and corticotropin-releasing factor as two peptides that act independently and interdependently to influence DR-5-HT function. The role of non-serotonergic components of the DR in translating the effect of each of these peptides is discussed. This synthesis refines our views on the regulation of the DR-5-HT system and importantly, gives insight into mechanisms of endogenous control of DR function, the dysregulation of which may contribute to pathophysiology.
Valentino
R J
RJ
Department of Anesthesiology and Critical Care Medicine, 402C Abramson Pediatric Research Ctr, The Children's Hospital of Philadelphia, Osler Cr, Philadelphia, PA 19104, USA. valentino@email.chop.edu
Commons
K G
KG
D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D006801:Humans; D009479:Neuropeptides / Q000502:physiology*; D011903:Raphe Nuclei / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*
D009479:Neuropeptides; D012701:Serotonin