Does increased endogenous CCK interact with serotonin to reduce food intake in rats?
The present study was aimed to test the hypothesis that increased endogenous CCK may interact with the anorectic serotonergic agent dl-fenfluramine to reduce food intake in rats. Previous studies, using selective CCK receptor antagonists, could demonstrate CCK-dependent 5-HT-induced anorexia. In the present approach, we used protease inhibitors to increase levels of endogenous CCK instead of blocking CCK receptors by antagonists. The protease inhibitors we used were soybean trypsin inhibitor (STI) and camostate. We hypothesized that combining the anorectic serotonergic drug dl-fenfluramine with either STI or camostate should result in an enhanced hypophagic effect when compared to single drug treatment. All feeding experiments were performed in non-deprived rats during night time feeding. Given alone, STI (500 mg/kg, po), camostate (200 mg/kg po) and also fenfluramine (1-9 mg/kg ip) reduced significantly food intake, with a more pronounced effect following fenfluramine. However, the experiments do not provide evidence for any additive or synergistic action between camostate or STI and the anorectic serotonergic drug dl-fenfluramine on food intake.
Voigt
J P
JP
Institute of Pharmacology and Toxicology, Charité, Humboldt University, D-10098 Berlin, Germany. joerg-peter.voigt@charite.de
Wenz
D
D
Voits
M
M
Fink
H
H
D000818:Animals; D000855:Anorexia / Q000209:etiology; D001835:Body Weight / Q000187:drug effects; D002766:Cholecystokinin / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects; D004952:Esters; D005277:Fenfluramine / Q000494:pharmacology; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013997:Time Factors; D014361:Trypsin Inhibitors / Q000494:pharmacology
D002766:Cholecystokinin; D004952:Esters; D005277:Fenfluramine; D016670:Gabexate; D006146:Guanidines; D011480:Protease Inhibitors; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014361:Trypsin Inhibitors; C034532:camostat