title: Cannabinoid CB₁ receptor restrains accentuated activity of hypothalamic corticotropin-releasing factor and brainstem tyrosine hydroxylase neurons in endotoxemia-induced hypophagia in rats.
abstract: It is well known that endocannabinoids play an important role in the regulation of food intake and body weight. Endocannabinoids and cannabinoid receptors are found in the hypothalamus and brainstem, which are central areas involved in the control of food intake and energy expenditure. Activation of these areas is related to hypophagia observed during inflammatory stimulus. This study investigated the effects of cannabinoid (CB₁) receptor blockade on lipopolysaccharide (LPS)-induced hypophagia. Male Wistar rats were pretreated with rimonabant (10 mg/kg, by gavage) or vehicle; 30 min later they received an injection of either LPS (100 μg/kg, intraperitoneal) or saline. Food intake, body weight, corticosterone response, CRF and CART mRNA expression, Fos-CRF and Fos-α-MSH immunoreactivity in the hypothalamus and Fos-tyrosine hydroxylase (TH) immunoreactivity in the brainstem were evaluated. LPS administration decreased food intake and body weight gain and increased plasma corticosterone levels and CRF mRNA expression in the PVN. We also observed an increase in Fos-CRF and Fos-TH double-labeled neurons after LPS injection in vehicle-pretreated rats, with no changes in CART mRNA or Fos-α-MSH immunoreactive neurons in the ARC. In saline-treated animals, rimonabant pretreatment decreased food intake and body weight gain but did not modify hormone response or Fos expression in the hypothalamus and brainstem compared with vehicle-pretreated rats. Rimonabant pretreatment potentiated LPS-induced hypophagia, body weight loss and Fos-CRF and Fos-TH expressing neurons. Rimonabant did not modify corticosterone, CRF mRNA or Fos-α-MSH responses in rats treated with LPS. These data suggest that the endocannabinoid system, mediated by CB₁ receptors, modulates hypothalamic and brainstem circuitry underlying the hypophagic effect during endotoxemia to prevent an exaggerated food intake decrease. This article is part of a Special Issue entitled 'Central Control of Food Intake'.
authors.affiliation: Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Rorato
authors.forename: Wagner Luis
authors.initials: WL
authors.lastname: Reis
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Carvalho Borges
authors.forename: José
authors.initials: J
authors.lastname: Antunes-Rodrigues
authors.forename: Lucila Leico Kagohara
authors.initials: LL
authors.lastname: Elias
mesh_terms: D000818:Animals; D000856:Anorexia Nervosa / Q000209:etiology / Q000473:pathology*; D001835:Body Weight / Q000187:drug effects; D001933:Brain Stem / Q000473:pathology*; D002452:Cell Count; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D019446:Endotoxemia / Q000139:chemically induced / Q000150:complications; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000235:genetics / Q000378:metabolism; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D016761:Oncogene Proteins v-fos / Q000235:genetics / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D016761:Oncogene Proteins v-fos; D010880:Piperidines; D011720:Pyrazoles; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D009074:Melanocyte-Stimulating Hormones; D003346:Corticotropin-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase; D000077285:Rimonabant; D003345:Corticosterone