Urocortin 1 in the dorsal raphe regulates food and fluid consumption, but not ethanol preference in C57BL/6J mice

Neuroscience. 2006;137(4):1439-45. doi: 10.1016/j.neuroscience.2005.10.021. Epub 2005 Dec 9.

Abstract

The midbrain-localized Edinger-Westphal nucleus is a major site of production of urocortin 1. Urocortin 1 is a neuropeptide related to corticotropin-releasing factor that has high affinity for corticotropin-releasing factor type-1 and corticotropin-releasing factor type-2 receptors. In several mouse models, the amount of urocortin 1 neurons within the Edinger-Westphal nucleus is positively associated with ethanol preference. Central administration of urocortin 1 exerts potent anorectic actions, and implicates endogenous urocortin 1 in the regulation of food intake. It is possible that brain areas such as the dorsal raphe, which receives urocortin 1 from the Edinger-Westphal nucleus and highly expresses corticotropin-releasing factor type-2 receptors, mediate the actions of urocortin 1 on feeding and ethanol preference. In this study the amount of food, water and ethanol consumed over the dark cycle by ethanol-preferring C57BL/6J mice was measured after injection of artificial cerebrospinal fluid vehicle, urocortin 1, corticotropin-releasing factor and the corticotropin-releasing factor type-2 receptor-selective antagonist antisauvagine-30 onto the dorsal raphe. Compared with vehicle, corticotropin-releasing factor and antisauvagine-30, urocortin 1 induced a significant reduction in the amount of food consumed overnight. Also, compared with antisauvagine-30 treatment, urocortin 1 significantly reduced the amount of weight gained during this time. Urocortin 1 also significantly reduced the total amount of fluid consumed, but did not alter ethanol preference, which was high during all treatments. These results suggest that the dorsal raphe is a neuroanatomical substrate of urocortin 1-induced reductions in feeding, possibly through modulation of serotonergic activity from this nucleus. In addition, it is suggested that endogenous urocortin 1 in this area, such as from the Edinger-Westphal nucleus, does not regulate ethanol preference in C57BL/6J mice.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcohol Drinking*
  • Animals
  • Appetite / physiology*
  • Corticotropin-Releasing Hormone / physiology*
  • Drinking Behavior / physiology*
  • Ethanol*
  • Feeding Behavior / physiology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microinjections
  • Peptides / administration & dosage
  • Peptides / pharmacology
  • Raphe Nuclei / physiology*
  • Rats
  • Urocortins
  • Weight Gain / physiology

Substances

  • Peptides
  • Urocortins
  • Ethanol
  • Corticotropin-Releasing Hormone