Cholecystokinin and hypothalamic corticotrophin-releasing factor participate in endotoxin-induced hypophagia.
Cholecystokinin (CCK) provides a meal-related signal that activates brainstem neurons, which have reciprocal interconnections with the hypothalamic paraventricular nucleus. Neurons that express corticotrophin-releasing factor (CRF) in the hypothalamus possess anorexigenic effects and are activated during endotoxaemia. This study investigated the effects of CCK(1) receptor blockade on lipopolysaccharide (LPS)-induced hypophagia and hypothalamic CRF neuronal activation. Male Wistar rats were pretreated with a specific CCK(1) receptor antagonist (devazepide; 1 mg kg(-1); i.p.) or vehicle; 30 min later they received LPS (100 μg kg(-1); i.p.) or saline injection. Food intake, corticosterone responses and Fos-CRF and Fos-α-melanocyte-stimulating hormone (α-MSH) immunoreactivity in the hypothalamus and Fos-tyrosine hydroxylase immunoreactivity in the nucleus of the solitary tract (NTS) were evaluated. In comparison with saline treatment, LPS administration decreased food intake and increased plasma corticosterone levels, as well as the number of Fos-CRF and Fos- tyrosine hydroxylase double-labelled neurons in vehicle-pretreated rats; no change in Fos-α-MSH immunoreactivity was observed after LPS injection. In saline-treated animals, devazepide pretreatment increased food intake, but it did not modify other parameters compared with vehicle-pretreated rats. Devazepide pretreatment partly reversed LPS-induced hypophagia and Fos-CRF and brainstem neuronal activation. Devazepide did not modify the corticosterone and Fos-α-MSH responses in rats treated with LPS. In conclusion, the present data suggest that LPS-induced hypophagia is mediated at least in part by CCK effects, via CCK(1) receptor, on NTS and hypothalamic CRF neurons.
Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirao Preto, Sao Paulo, Brazil.
Rodrigo
R
Rorato
Wagner Luis
WL
Reis
José
J
Antunes-Rodrigues
Lucila Leico Kagohara
LL
Elias
D000818:Animals; D001933:Brain Stem / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D020109:Devazepide / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D006963:Hyperphagia / Q000139:chemically induced / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010906:Pituitary Hormone-Releasing Hormones / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors / Q000378:metabolism; D017552:Solitary Nucleus / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000521:alpha-MSH / Q000378:metabolism
D004731:Endotoxins; D008070:Lipopolysaccharides; D010906:Pituitary Hormone-Releasing Hormones; D016760:Proto-Oncogene Proteins c-fos; D043886:Receptor, Cholecystokinin A; D000521:alpha-MSH; D002766:Cholecystokinin; D003346:Corticotropin-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase; D020109:Devazepide; D003345:Corticosterone