کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2537043 1559174 2006 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Early tolerance to the hypophagic effect of the cannabinoid receptor antagonist SR141716 does not impede blockade of an orexigenic stimulus
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Early tolerance to the hypophagic effect of the cannabinoid receptor antagonist SR141716 does not impede blockade of an orexigenic stimulus
چکیده انگلیسی

The cannabinoid CB1 receptor antagonist SR141716 (Rimonabant®) is known to reduce food intake by central and peripheral mechanisms. Recently, SR141716 has been reported to block the orexigenic effect of ghrelin, a potent orexigenic peptide produced by the stomach.This study investigated whether in rats, made tolerant to the hypophagic effect of SR141716, the drug was still capable to block the orexigenic activity of another non-natural (hypothalamic) peptide, i.e., the growth hormone releasing peptide (GHRP) hexarelin, a ghrelin mimetic.In the acute experiments, each dose of SR141716 (1, 5 and 10 mg/kg i.p.) reduced food intake with respect to vehicle-treated rats, whereas hexarelin (160 μg/kg s.c.) markedly stimulated feeding. All doses of SR141716 were capable to reduce the orexigenic effect of the GHRP. A 15-day administration of SR141716 (10 mg/kg i.p.) reduced both food intake and body weight. Tolerance to the hypophagic effect of SR141716 developed within 5 days, but in contrast, body weight remained markedly below that of vehicle-treated group throughout the entire treatment period. Interestingly, despite development of tolerance to its hypophagic effect, SR141716 was capable to suppress the orexigenic effect of repeated hexarelin challenge tests performed throughout the chronic experiments.In conclusion, the results of the present study confirm and broaden the existence of a functional relationship between ghrelin and endocannabinoids in the control of food intake, and bespeak the ability of a CB1 receptor antagonist to suppress orexia caused by stimuli alien to direct stimulation of the cannabinoid system.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 542, Issues 1–3, 7 August 2006, Pages 116–120
نویسندگان
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