AJP - Regulatory, Integrative and Comparative Physiology, Vol 251, Issue 4 718-R723, Copyright © 1986 by American Physiological Society
Intracranial infusion of CCK-8 derivatives suppresses food intake in rats
T. Mori, K. Nagai, H. Nakagawa and N. Yanaihara
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.
