Reciprocal interaction of 5-hydroxytryptamine and cholecystokinin in the control of feeding patterns in rats.
1. The effect of the CCKA receptor antagonist, devazepide (100 mg kg-1) on meal parameters during the initial phase of the dark period was studied in free-feeding rats by use of a procedure for continuously monitoring feeding patterns. 2. In a second experiment, the effect of devazepide on the reduction in meal parameters induced by the 5-hydroxytryptamine (5-HT) releaser and uptake inhibitor, (+)-fenfluramine (1.5 mg kg-1) in 4 h food-deprived rats was examined. 3. The hypophagic effect of an intraperitoneal injection of cholecystokinin (CCK-8, 4 micrograms kg-1) was studied in rats treated with the 5-HT receptor antagonist, metergoline (1 and 2 mg kg-1). 4. Devazepide increased the size of the first meal in free-feeding, but not in 4 h food-deprived rats and partially antagonized the effect of (+)-fenfluramine on the size and duration of the first meal. The reduction in eating rate induced by (+)-fenfluramine was not modified by devazepide. No changes in (+)-fenfluramine or (+)-norfenfluramine levels were found in the brain of rats treated with devazepide. 5. The effect of CCK-8 on meal size was completely antagonized by 2 mg kg-1 metergoline. A significant interaction was also found between 2 mg kg-1 metergoline and CCK-8 as regards their effect on the inter-meal interval. 6. The results suggest a reciprocal interaction between 5-HT and CCK-8 in enhancing the satiating effect of food in rats.
Grignaschi
G
G
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Mantelli
B
B
Fracasso
C
C
Anelli
M
M
Caccia
S
S
Samanin
R
R
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020109:Devazepide; D005247:Feeding Behavior / Q000187:drug effects*; D005277:Fenfluramine / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012528:Satiety Response / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*
D001570:Benzodiazepinones; D008711:Metergoline; D005277:Fenfluramine; D012701:Serotonin; D002766:Cholecystokinin; D020109:Devazepide