Urocortin 1 in the dorsal raphe regulates food and fluid consumption, but not ethanol preference in C57BL/6J mice.
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.
Weitemier
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AZ
Department of Behavioral Neuroscience, Oregon Health and Science University and Portland Alcohol Research Center, Portland, OR 97239, USA. weitemier@brain.riken.jp
Ryabinin
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AE
D000428:Alcohol Drinking; D000818:Animals; D001066:Appetite / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D004327:Drinking Behavior / Q000502:physiology*; D000431:Ethanol; D005247:Feeding Behavior / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology; D011903:Raphe Nuclei / Q000502:physiology*; D051381:Rats; D054832:Urocortins; D015430:Weight Gain / Q000502:physiology
D010455:Peptides; D054832:Urocortins; D000431:Ethanol; D003346:Corticotropin-Releasing Hormone