Intracranial infusion of CCK-8 derivatives suppresses food intake in rats.

The effects of infusions for approximately 1 wk of the synthetic COOH-terminal octapeptide of cholecystokinin (CCK-8) and its derivatives, pyroglutamyl-CCK-8 (pGlu-CCK-8) and glutaryl-CCK-8 (Glt-CCK-8), into the suprachiasmatic nucleus (SCN) of the hypothalamus of male Wistar rats on their feeding behavior under 12:12 light-dark cycle were examined. Infusion of CCK-8 (0.8 pmol/h) did not change the total daily food intake but caused slight decrease in food intake during the 12-h dark period with slight increase in the 12-h light period. Infusions of pGlu-CCK-8 (0.8 pmol/h) and Glt-CCK-8 (0.8 pmol/h) markedly reduced food intake during the 12-h dark period but had little effect in the light period and thus decreased total daily food intake. The reductions in food intake during the 12-h dark period due to infusions of the CCK-8 derivatives were greater than that due to CCK-8 infusion. Body weight changes reflected changes in food intake. CCK-8 derivatives appeared to suppress both meal size and frequency at the early part of the infusion period but reduce only meal size at the later part. Histological examination showed that infusion sites in the brain were widely damaged; however, neurons in the SCN appeared to be intact. These findings suggest that CCK-8 suppresses food intake during the dark period in rats by acting on some site(s) in the brain. The results also support the possibility that CCK-8 is degraded enzymatically in the brain, whereas the two derivatives, pGlu-CCK-8 and Glt-CCK-8, are resistant to degradation.