title: Systemic urocortin 2, but not urocortin 1 or stressin 1-A, suppresses feeding via CRF2 receptors without malaise and stress.
abstract: OBJECTIVE
  Infusion of corticotropin-releasing factor (CRF)/urocortin (Ucn) family peptides suppresses feeding in mice. We examined whether rats show peripheral CRF/Ucn-induced anorexia and determined its behavioural and pharmacological bases.
  
  
  METHODS
  Male Wistar rats (n= 5-12 per group) were administered (i.p.) CRF receptor agonists with different subtype affinities. Food intake, formation of conditioned taste aversion and corticosterone levels were assessed. In addition, Ucn 1- and Ucn 2-induced anorexia was studied in fasted CRF(2) knockout (n= 11) and wild-type (n= 13) mice.
  
  
  RESULTS
  Ucn 1, non-selective CRF receptor agonist, reduced food intake most potently (~0.32 nmol·kg(-1) ) and efficaciously (up to 70% reduction) in fasted and fed rats. The peptides' rank-order of anorexic potency was Ucn 1 ≥ Ucn 2 > >stressin(1) -A > Ucn 3, and efficacy, Ucn 1 > stressin(1) -A > Ucn 2 = Ucn 3. Ucn 1 reduced meal frequency and size, facilitated feeding bout termination and slowed eating rate. Stressin(1) -A (CRF(1) agonist) reduced meal size; Ucn 2 (CRF(2) agonist) reduced meal frequency. Stressin(1) -A and Ucn 1, but not Ucn 2, produced a conditioned taste aversion, reduced feeding efficiency and weight regain and elicited diarrhoea. Ucn 1, but not Ucn 2, also increased corticosterone levels. Ucn 1 and Ucn 2 reduced feeding in wild-type, but not CRF(2) knockout, mice.
  
  
  CONCLUSIONS
  CRF(1) agonists, Ucn 1 and stressin(1) -A, reduced feeding and induced interoceptive stress, whereas Ucn 2 potently suppressed feeding via a CRF(2) -dependent mechanism without eliciting malaise. Consistent with their pharmacological differences, peripheral urocortins have diverse effects on appetite.
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Fekete
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: A
authors.initials: A
authors.lastname: Szücs
authors.forename: V
authors.initials: V
authors.lastname: Sabino
authors.forename: P
authors.initials: P
authors.lastname: Cottone
authors.forename: J
authors.initials: J
authors.lastname: Rivier
authors.forename: W W
authors.initials: WW
authors.lastname: Vale
authors.forename: G F
authors.initials: GF
authors.lastname: Koob
authors.forename: E P
authors.initials: EP
authors.lastname: Zorrilla
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000502:physiology; D005247:Feeding Behavior; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010456:Peptides, Cyclic / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000502:physiology*; D013312:Stress, Physiological; D054832:Urocortins / Q000502:physiology*
chemical_list: C101531:CRF receptor type 2; D010456:Peptides, Cyclic; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C519520:cyclo(31-34)(phenylalanyl(12)-norleucyl(21,28)-glutamyl(31)-lysyl(34))acetyl-corticotropin releasing factor (4-41); C514216:urocortin 3, rat; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone