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Systemic urocortin 2, but not urocortin 1 or stressin 1-A, suppresses feeding via CRF2 receptors without malaise and stress. Br J Pharmacol 2011 Dec;164(8):1959-75

Date

06/02/2011

Pubmed ID

21627635

Pubmed Central ID

PMC3246660

DOI

10.1111/j.1476-5381.2011.01512.x

Scopus ID

2-s2.0-81855228892 (requires institutional sign-in at Scopus site)   36 Citations

Abstract

BACKGROUND AND PURPOSE: 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.

EXPERIMENTAL APPROACH: 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.

KEY 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 AND IMPLICATIONS: 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.

Author List

Fekete EM, Zhao Y, Szücs A, Sabino V, Cottone P, Rivier J, Vale WW, Koob GF, Zorrilla EP

Author

Eva M. Fekete PhD Research Scientist I in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Corticosterone
Corticotropin-Releasing Hormone
Feeding Behavior
Female
Male
Mice
Mice, Knockout
Peptides, Cyclic
Rats
Rats, Wistar
Receptors, Corticotropin-Releasing Hormone
Stress, Physiological
Urocortins