ELEVATION OF FEED-INTAKE IN PARASITE-INFECTED LAMBS BY CENTRAL ADMINISTRATION OF A CHOLECYSTOKININ RECEPTOR ANTAGONIST

The role of cholecystokinin (CCK) in modulating feed intake depression in parasite-infected lambs was investigated using CCK receptor antago nists (L364-718 and loxiglumide). Four experiments were carried out us ing ewe lambs infected with 4000 Trichostrongylus colubriformis larvae /d or non-infected controls (n8, live weight 25 kg). Animals were fed daily on a nutritionally complete pelleted diet and had free access to water. In the first experiment, infected and non-infected animals wer e injected subcutaneously with CCK antagonist (100 mu g L364-718) or c arrier alone as a single dose. In the second experiment, CCK antagonis t (loxiglumide: 0, 5, 10 or 20 mg/kg live weight) was injected into a jugular vein immediately before feeding. In the third experiment, anim als were infused continuously with the CCK antagonist (loxiglumide; 10 mg/kg per h) for 10 min before feeding and for the first 2 h of feedi ng. In the final experiment, lambs were fitted with an indwelling cere bral ventricular cannula and infused with a CCK antagonist (loxiglumid e, 162 mu g/min), CCK agonist (CCK-8, 2.5 pmol/min), loxiglumide plus CCK-8 or sterile saline solution alone via the cannula for 30 min befo re feeding and for the first 60 min of feeding. In all the experiments short-term feed intake was recorded at 10 and 15 min intervals for th e first; and second hours of feeding respectively, then at hourly inte rvals for the remainder of the 8 h recording period. Peripheral inject ion with L364-718 or loxiglumide did not elevate feed intake in either the infected or non-infected animals. However, feed intake was increa sed (P < 0.05) in the short term by central infusion of loxiglumide, t his effect being greater in the infected animals and apparently due to an elevation in intake during the second hour of feeding. CCK-8 depre ssed short term feed intake only in the infected animals (P < 0.05). T otal daily feed consumption was not influenced by any of the pharmacol ogical agents. The results indicate an involvement of central CCK rece ptors in regulation of feed intake depression following gastrointestin al parasitism of sheep and the possibility of a similar role in non-in fected sheep. They do not support the singular importance of a periphe ral action of CCK in determining satiety.