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Original Paper

Cocaine- and Amphetamine-Related Transcript Is Involved in the Orexigenic Effect of Endogenous Anandamide

Osei-Hyiaman D.a · Depetrillo M.a · Harvey-White J.a · Bannon A.W.b · Cravatt B.F.c · Kuhar M.J.d · Mackie K.e · Palkovits M.f · Kunos G.a

Author affiliations

aSection on Neuroendocrinology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Md., bAmgen Inc., Neuroscience, Thousand Oaks, Calif., cScripps Institute, La Jolla, Calif., dYerkes National Primate Research Center, Division of Neuroscience, Emory University, Atlanta, Ga., eDepartments of Physiology and Anesthesiology, University of Washington, Seattle, Wash., and fLaboratory of Genetics, National Institute on Mental Health, National Institutes of Health, Bethesda, Md., USA

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Neuroendocrinology 2005;81:273–282

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: April 25, 2005
Accepted: July 03, 2005
Published online: September 27, 2005
Issue release date: September 2005

Number of Print Pages: 10
Number of Figures: 8
Number of Tables: 0

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN

Abstract

Endocannabinoids acting at CB1 cannabinoid receptors (CB1) increase appetite. In view of the predominant presynaptic localization of CB1 in the brain, we tested the hypothesis that the orexigenic effect of endocannabinoids involves inhibition of the release of a tonically active anorexigenic mediator, such as the peptide product of the cocaine- and amphetamine-related transcript (CART). The CB1 antagonist rimonabant inhibited food intake in food-restricted wild-type mice, but not in their CART-deficient littermates. Mice deficient in fatty acid amide hydrolase (FAAH), the enzyme responsible for the in vivo metabolism of the endocannabinoid anandamide, have reduced levels of CART-immunoreactive nerve fibers and terminals in several brain regions implicated in appetite control, including the arcuate, dorsomedial and periventricular nuclei of the hypothalamus, the amygdala, the bed nucleus of the stria terminalis and the nucleus accumbens, and treatment of FAAH–/– mice with rimonabant, 3 mg/kg/day for 7 days, increased CART levels toward those seen in FAAH+/+ wild-type controls. In contrast, no difference in the density of CART-immunoreactive fibers was observed in the median eminence and the paraventricular nucleus of FAAH+/+ and FAAH–/– mice. Acute treatment of wild-type mice with the cannabinoid agonist HU-210 resulted in elevated CART levels in the dorsomedial nucleus and the shell portion of the nucleus accumbens. These observations are compatible with CART being a downstream mediator of the CB1-mediated orexigenic effect of endogenous anandamide.

© 2005 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: April 25, 2005
Accepted: July 03, 2005
Published online: September 27, 2005
Issue release date: September 2005

Number of Print Pages: 10
Number of Figures: 8
Number of Tables: 0

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN


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