Pergamon Pharmacology Biochemistry and Behavior, Vol. 48, No. 2, pp. 479-486, 1994 Copyright © 1994 Elsevier Science Ltd Printed in the USA. All rights reserved 0091-3057/94 $6.00 + .00 0091-3057(93)E0074-E Effects of the CCK Receptor Antagonist MK-329 on Food Intake in Broiler Chickens M. COVASA' AND J. M. FORBES Department of Animal Physiology and Nutrition, University of Leeds, Leeds LS2 9JT, UK Received 15 March 1993 COVASA, M. AND J. M. FORBES. Effects of the CCK receptorantagonistMK-329on food intake in broilerchickens. PHARMACOL BIOCHEM BEHAV 48(2) 479--486, 1994.-The cholecystokinin (CCK) receptor antagonist MK-329 (pre- viously L-364,718) was administered intraperitoneally to free-feeding broiler chickens and tested for conditioning effects using the colored food paradigm. The 8.0, 16.0, and 32.0 pg/kg doses of MK-329 did not exert any effect on food intake and failed to condition a color preference or aversion. When higher doses were used (90, 180, and 360/tg/kg) MK-329 caused a significant increase in food intake during the 2-h test period. Intravenously injected MK-329 (70, 140, and 280/~g/kg) produced an increase in food intake, with maximum increases occurring at a dose of 70/~g/kg. CCK (14/~g/kg) caused a reduction in feeding, and this effect was not blocked by pretreatment with intraperitoneal injection of MK-329 (32, 90, 180, and 360 ttg/kg). The results question the role of endogenous CCK in satiety in chickens. Cholecystoidnin MK-329 Chickens Conditioning Preference test Satiety CCK has been reported to inhibit food consumption in a vari- ety of species, including rat, mouse, hamster, dog, pig, sheep, wolf, chicken, monkey, and humans (1,15,20,26,28,29,37,40, 47,56). The mechanism mediating the satiety action of CCK has been extensively investigated in rats and, to a lesser extent, in chickens. Evidence indicates that CCK, released from the intestine after a meal, acts on receptors in the gut, relaying sensory information via the vagus nerves to brain regions reg- ulating feeding behaviours (9,11,12,19,31,39,44,52,53,58). Considerable debate has taken place on whether the effect of exogenous CCK on food intake is physiological or pharma- cological, whether changes in food intake are secondary to CCK-induced malaise as opposed to satiety per se, and whether the effects are central or peripheral in origin (2,21, 41,55,57). If the hypothesis that CCK acts as a satiety factor is correct, it should follow that administration of a specific antagonist to CCK would block the effect of endogenous CCK released during a meal and, thus, increase the amount of food consumed. Recent studies with MK-329 (previously named L- 364,718), a potent antagonist of the CCK-A receptor, which is found mainly in peripheral tissues, have demonstrated an increase in food intake in nonfasted rats (16,24,27), pigs (17), and humans (59). As with CCK itself, the effect of the antago- nist is dependent upon the paradigm (dose, strain, age, type of food, time of day, fasted vs. nonfasted, prefed vs. no pre- feeding) (51). Several studies showed that chicks are capable of appro- priate food selection (23) and that they associate general feed- ing-related behaviors with beneficial consequences (60) and aversion to substances associated with long-term aversive con- sequences (45). Kutlu and Forbes (30) showed that chicks are capable of adjusting their intake of ascorbic acid to meet their requirements by means of color. The use of color supports findings that revealed that chickens have a strong ability to employ color in learning situations and that obtaining shifts away from color is very difficult (5,14,33). In our previous studies, which involved intraperitoneal injections of CCK, we showed that chickens can associate injections of exogenous CCK with one colored food and develop an aversion for the food color paired with CCK (8). Furthermore, the association with color was reversed as a result of pairing injections with reversed colored foods. No published studies have previously assessed the effect of MK-329 on food intake in chickens. Also, no studies have yet utilized the CCK antagonist MK-329 to investigate the possible physiological involvement of CCK using the conditioning col- ored food paradigm. GENERAL METHOD Day-old female broiler chicks were obtained from Mayfield Chicks Ltd. Rossendale, Lancs. They were fed standard ' To whom requests for reprints should be addressed. 479