Investigation of cholecystokinin-8s-induced hypophagia in neonatal broiler chicks: Roles of central adrenergic and serotonergic systems

Cholecystokinin (CCK) is integral to the central control of appetite, with its sulfated octapeptide isoform (CCK-8s) being particularly relevant. While CCK's anorexigenic effects have been established, the interactions between CCK-8s and adrenergic and serotonergic receptor subtypes in mediating food intake remain incompletely understood. This research was designed to examine the impact of centrally administered CCK-8s on food consumption in broilers, focusing on how it interacts with adrenergic and serotonergic receptors to influence intake. For this purpose, nine experiments were conducted on broilers. In experiment 1, broilers received central infusion of saline and CCK-8s (0.25, 0.5, and 1 nmol). The second experiment evaluated the effects of saline, the α1-adrenergic antagonist prazosin, CCK-8s at 1 nmol, and a combination of prazosin with CCK-8s. Experiments three through nine followed a similar design, substituting prazosin with other agents targeting different receptors, including the α2 antagonist yohimbine, β1 antagonist metoprolol, β2 antagonist ICI 118,551, serotonin synthesis inhibitor PCPA, serotonin reuptake inhibitor fluoxetine, 5-HT1A receptor agonist 8-OH-DPAT, and 5-HT2C receptor antagonist SB242084. Food intake was recorded cumulatively up to two hours after infusions. The outcomes demonstrated that CCK-8s (0.5 and 1 nmol) significantly decreased meal intake compared to controls (P < 0.05). Interestingly, administration of CCK-8s with fluoxetine significantly enhanced its appetite-suppressing effect (P < 0.05), whereas co-injections with SB242084, PCPA, or ICI 118,551 decreased this effect (P < 0.05). The data suggest that the anorexigenic influence of CCK-8s involves signaling pathways mediated by β2 adrenergic and 5-HT2C serotonergic receptors, offering fresh perspectives on neuropeptidergic regulation of feeding and highlighting the need for further detailed mechanistic studies.