Corticotropin-releasing factor (CRF) or CRF binding-protein ligand inhibitor administration suppresses food intake in mice and elevates body temperature in rats

Corticotropin-releasing factor (CRF) receptor agonist and CRF binding-prote in (CRF-BP) ligand inhibitor peptides both activate CRF systems but exert v ery distinct functional profiles in animal models of arousal, energy balanc e and emotionality. The present studies were designed to extend the dissimi lar efficacy profiles of central administration of a CRF agonist, r/h CRF(1 -41), versus a CRF-BP ligand inhibitor, r/h CRF(6-33), into mouse and rat m odels of energy balance in order to further explore in vivo efficacy of the se ligands in two separate animal species. In CD-1 mice, food intake was si gnificantly attenuated 3 h after acute administration of CRF(1-41) (0.007-0 .2 nmol), but not CRF(6-33). In obese Ob/Ob mice, both CRF(1-41) (0.007-0.2 nmol) and CRF(6-33) (0.02-2.3 nmol) significantly attenuated basal feeding over 3 h following acute peptide administration. In rats, CRF(1-41) (1 nmo l) and CRF(6-33) (1.5-7.7 nmol) infusion significantly increased rectal tem perature. In studies employing a telemetry apparatus, core temperature was also increased by CRF(1-41) (1 nmol) and CRF(6-33) (1.5 nmol), whereas only CRF(1-41) increased locomotor activity and heart rate. These results sugge st that CRF receptor agonist administration is capable of producing a globa l profile of negative energy balance by reducing food intake in mice and in creasing energy expenditure in rats. In contrast, CRF-BP ligand inhibitor a dministration appears to suppress food intake in a mouse strain selective m anner and to elevate rectal and core temperature in rats without accompanyi ng cardiovascular activation. (C) 2001 Elsevier Science B.V. All rights res erved.