Leptin receptor deficiency is associated with upregulation of cannabinoid 1 receptors in limbic brain regions

Authors

  • Panayotis K. Thanos,

    Corresponding author
    1. Behavioral Neuropharmacology and Neuroimaging Lab, Department of Medicine, Brookhaven National Lab, Upton, New York
    2. Department of Psychology, SUNY Stony Brook, Stony Brook, New York
    3. Neuroscience Program, SUNY Stony Brook, Stony Brook, New York
    4. Laboratory of Neuroimaging, NIAAA, NIH, Department of Health and Human Services, Bethesda, Maryland
    • Behavioral Neuropharmacology and Neuroimaging Lab, Department of Medicine, 30 Bell Avenue Brookhaven National Lab, Upton, New York 11973, USA
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  • Roberto C. Ramalhete,

    1. Behavioral Neuropharmacology and Neuroimaging Lab, Department of Medicine, Brookhaven National Lab, Upton, New York
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  • Michael Michaelides,

    1. Behavioral Neuropharmacology and Neuroimaging Lab, Department of Medicine, Brookhaven National Lab, Upton, New York
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  • Yianni K. Piyis,

    1. Behavioral Neuropharmacology and Neuroimaging Lab, Department of Medicine, Brookhaven National Lab, Upton, New York
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  • Gene-Jack Wang,

    1. Behavioral Neuropharmacology and Neuroimaging Lab, Department of Medicine, Brookhaven National Lab, Upton, New York
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  • Nora D. Volkow

    1. Laboratory of Neuroimaging, NIAAA, NIH, Department of Health and Human Services, Bethesda, Maryland
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  • This article is a US Government work and, as such, is in the public domain in the United States of America.

Abstract

Leptin receptor dysfunction results in overeating and obesity. Leptin regulates hypothalamic signaling that underlies the motivation to hyperphagia, but the interaction between leptin and cannabinoid signaling is poorly understood. We evaluated the role of cannabinoid 1 receptors (CB1R) in overeating and the effects of food deprivation on CB1R in the brain. One-month-old Zucker rats were divided into unrestricted and restricted (fed 70% of unrestricted rats) diet groups and maintained until adulthood (4 months). Levels of relative binding sites of CB1R (CB1R binding levels) were assessed using [3H] SR141716A in vitro autoradiography. These levels were higher (except cerebellum and hypothalamus) at 4 months than at 1 month of age. One month CB1R binding levels for most brain regions did not differ between Ob and Lean (Le) rats (except in frontal and cingulate cortices in Le and in the hypothalamus in Ob). Four month Ob rats had higher CB1R binding levels than Le in most brain regions and food restriction was associated with higher CB1R levels in all brain regions in Ob, but not in Le rats. CB1R binding levels increased between adolescence and young adulthood which we believe was influenced by leptin and food availability. The high levels of CB1R in Ob rats suggest that leptin's inhibition of food-intake is in part mediated by downregulation of CB1R and that leptin interferes with CB1R upregulation under food-deprivation conditions. These results are consistent with prior findings showing increased levels of endogenous cannabinoids in the Ob rats corroborating the regulation of cannabinoid signaling by leptin. Synapse 62:637–642, 2008. Published 2008 Wiley-Liss, Inc.

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