Infusion of cholecystokinin between meals into free-feeding rats fails to prolong the intermeal interval

Abstract

The sulfated octapeptide of cholecystokinin (CCK-8) was infused intraperitoneally into 7 free-feeding male Sprague Dawley rats over a 6-day period. Infusions were given near the end of each free-feeding meal (1.87 μg/meal/rat), and also during the intermeal interval in gradually increasing doses (0.10-0.63 μg/5 min/rat). Food intake was continuously monitored and the infusions were controlled by microcomputer. Meal patterns, total food intake, and body weights during drug infusion were compared with data collected during a baseline period when only saline was infused. Meal-contingent CCK-8 infusion produced a significant 29.9% decrease in meal size which persisted throughout the drug-infusion period. Intermeal infusion of CCK-8 failed to prolong the intermeal interval (IMI) but it did initially prevent the compensatory decrease in IMI and increased feeding frequency expected after meal size was reduced. By the last day of drug infusion, total daily food intake recovered to baseline levels due to increased feeding frequency. Body weight was only transiently reduced by CCK-8 infusion. These findings show that (1) tolerance does not develop to the action of CCK-8 to suppress meal size, and (2) the administration of exogenous CCK-8 to free-feeding rats does not persistently prolong the intermeal interval.