Rimonabant induced anorexia in rodents is not mediated by vagal or sympathetic gut afferents

The selective CB1 receptor antagonist rimonabant is a novel weight control agent. Although CB1 receptors and binding sites are present in both the rodent central and peripheral nervous systems, including the afferent vagus nerve, the role of gut afferents in mediating anorexia following CB1R blockad...

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Bibliographic Details
Published in:Neuroscience letters 2009-01, Vol.449 (1), p.20-23
Main Authors: Madsen, Andreas N., Jelsing, Jacob, van de Wall, Esther H.E.M., Vrang, Niels, Larsen, Philip J., Schwartz, Gary J.
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Anorexia - chemically induced
Anorexia - physiopathology
Biological and medical sciences
Eating - drug effects
Eating - physiology
Food intake
Fundamental and applied biological sciences. Psychology
Ganglia, Sympathetic - physiology
Ganglionectomy - methods
Male
Meal pattern
Medical sciences
Metabolic diseases
Mice
Mice, Inbred C57BL
Obesity
Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ
Piperidines
Pyrazoles
Rats
Rats, Sprague-Dawley
Stilbamidines - metabolism
Vagotomy
Vagotomy - methods
Vagus Nerve - physiology
Vagus Nerve - surgery
Vertebrates: nervous system and sense organs
Visceral afferents
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Summary:The selective CB1 receptor antagonist rimonabant is a novel weight control agent. Although CB1 receptors and binding sites are present in both the rodent central and peripheral nervous systems, including the afferent vagus nerve, the role of gut afferents in mediating anorexia following CB1R blockade is still debated. In the present study we examined rimonabant-induced anorexia in male C57BL/6J mice with subdiaphragmatic vagotomy (VGX) as well as in male Sprague–Dawley rats subjected to either subdiaphragmatic vagal deafferentation (SDA) alone or in combination with a complete celiac–superior mesenteric ganglionectomy (CGX). Irrespective of the operational procedure, rimonabant (10 mg/kg) effectively reduced standard chow as well as palatable diet (ensure) intake. In conclusion, the data clearly demonstrate that neither vagal gut afferents, nor gut afferents traveling via the sympathetic nervous system, are required for rimonabant to inhibit food intake leading to the hypothesis that centrally located CB1 receptors are the prime mediators of rimonabant-induced anorexia.
ISSN:0304-3940
1872-7972
DOI:10.1016/j.neulet.2008.10.001