Abstract
Corticotropin-releasing factor (CRF) has been hypothesized to modulate consummatory behavior through the Type 2 CRF (CRF2) receptor. However, behavioral functions subserved by the CRF2 receptor remain poorly understood. Recently, human urocortin II (hUcn II), a selective CRF2 receptor agonist, was identified. To study the effects of this neuropeptide on ingestive behavior, we examined the effects of centrally infused hUcn II (i.c.v. 0, 0.01, 0.1, 1.0, 10.0 μg) on the microstructure of nose-poke responding for food and water in nondeprived, male rats. Malaise-inducing properties of the peptide were monitored using conditioned taste aversion (CTA) testing. To identify potential sites of action, central induction of Fos protein expression was examined. hUcn II dose dependently reduced the quantity and duration of responding for food and water at doses lower (0.01–1.0 μg) than that forming a CTA (10 μg). Effects were most evident during hours 4 to 6 of the dark cycle. Meal pattern analysis showed that hUcn II potently (0.1 μg) increased the satiating value of food. Rats ate and drank smaller and shorter meals without changing meal frequency. Rats also ate more slowly. hUcn II induced Fos in regions involved in visceral sensory processing and autonomic/neuroendocrine regulation and resembling those activated by appetite suppressants. hUcn II is a promising neuropeptide for investigating the role of the CRF2 receptor in ingestive behavior.
Footnotes
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This work was supported by DK26741 from the National Institute of Diabetes and Digestive and Kidney Diseases. G.R.V. was supported by AA05563, an Individual National Research Service Award from the National Institute of Alcohol Abuse and Alcoholism. E.P.Z. was supported by a Minority Research Supplement to DK26741.
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DOI: 10.1124/jpet.102.047712
- Abbreviations:
- CRF
- corticotropin-releasing factor
- hUcn II
- human urocortin II
- d-Phe CRF12–41
- [d-Phe12, Nle21,38 Cα MeLeu37] rat/human CRF12–41
- CTA
- conditioned taste aversion
- Ucn
- urocortin
- mUcn II
- murine urocortin II
- ANOVA
- analysis of variance
- MED
- minimum effective dose
- CeA
- central nucleus of the amygdala
- NTS
- nucleus of the solitary tract
- SKF 38393
- 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
- Received December 4, 2002.
- Accepted December 10, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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