CCK - 8 and CCK - 58 differ in their effects on nocturnal solid meal 1 pattern in undisturbed rats

26 Various molecular forms of cholecystokinin (CCK) reduce food intake in rats. Although CCK-8 is the 27 most studied form, we reported that CCK-58 is the only detectable endocrine peptide form in rats. We 28 investigated the dark phase rat chow intake pattern following injection of CCK-8 and CCK-58. Ad libitum 29 fed male Sprague-Dawley rats were intraperitoneally injected with CCK-8, CCK-58 (0.6, 1.8 and 5.2 30 nmol/kg), or vehicle. Food intake pattern was assessed during the dark phase using an automated weighing 31 system allowing continuous undisturbed monitoring of physiologic eating behavior. Both CCK-8 and 32 CCK-58 dose-dependently reduced 1-h dark phase food intake with an equimolar dose of 1.8 nmol being 33 similarly effective (-49% and -44%). CCK-58 increased the latency to the first meal, whereas CCK-8 did 34 not. The inter-meal interval was reduced after CCK-8 (1.8 nmol/kg, -41%) but not after CCK-58. At this 35 dose, CCK-8 increased the satiety ratio by 80% and CCK-58 by 160%, respectively, compared to vehicle. 36 When behavior was assessed manually, CCK-8 reduced locomotor activity (-31%), whereas grooming 37 behavior was increased (+59%). CCK-58 affected neither grooming nor locomotor activity. In conclusion, 38 reduction of food intake by CCK-8 and CCK-58 is achieved by differential modulation of food intake 39 microstructure and behavior. These data highlight the importance of studying the molecular forms of 40 peptides that exist in vivo in tissue and circulation of the animal being studied. 41 42