CCK8 neurons of the ventromedial (VMH) hypothalamus mediate the upper gut motor changes associated with feeding in rats.

The effect of microinfusions of cholecystokinin octapeptide (CCK8) and its antagonist L364,718 on duodenal and jejunal motility were evaluated by electromyography in fasted and fed rats. The rats were chronically fitted with electrodes implanted on the duodeno-jejunal wall. Steel cannulas were placed bilaterally in either the ventromedial (VMH) and lateral (LHA) hypothalamus. In 8 h fasted rats, microinfusion of CCK8 (1 ng/kg) into the VMH disrupted the migrating myoelectric complex (MMC) and replaced it by irregular spiking activity for 45.0 +/- 4.9 min at the duodenal level without affecting the jejunal MMC pattern. The duration of these effects were dose-related between 1 and 50 ng/kg. When injected into the LHA at 1, 10 or 50 ng/kg, CCK8 had no effect on either duodenal or jejunal motility. When infused bilaterally into the VMH 10 min before feeding, L364,718 (1 or 10 micrograms/kg) significantly reduced the duration of the postprandial disruption of MMCs by 29.1% and 35.9%, respectively, in the duodenum but not the jejunum (P less than 0.05). Infused into the LHA at similar and higher dosages (1 and 10 micrograms/kg) L364,718 had no effect on the duration of the duodeno-jejunal fed pattern. These results suggest that, in rats, (i) CCK8 is involved in the maintenance of the typical postprandial disruption of duodenal MMCs observed after a meal, and (ii) these effects are selectively mediated through CCK8 receptors located in the ventromedial hypothalamic nuclei.