GASTRIC LOADS AND CHOLECYSTOKININ SYNERGISTICALLY STIMULATE RAT GASTRIC VAGAL AFFERENTS

Both gastric preloads and exogenous cholecystokinin (CCK) administrati on inhibit food intake, and combinations of preloads and CCK suppress feeding to a greater degree than either stimulus delivered alone. A ro le for the vagus nerve in mediating CCK's inhibition of food intake ha s been proposed, and gastric vagal afferent fibers respond to both gas tric loads and local CCK infusions. To examine whether combined load a nd CCK stimuli may synergistically augment gastric neural afferent act ivity at the level of the peripheral vagus, we have examined the gastr ic vagal afferent responses (n = 8) to a range of gastric saline loads (1, 2, and 3 ml) and exogenous close celiac arterial CCK (10 and 100 pmol) when administered alone or in combination. Gastric loads ineffec tive in eliciting a significant increase in vagal afferent activity wh en administered alone became effective when combined with doses of CCK that were subthreshold for the production of a vagal afferent respons e. Gastric loads that alone were effective in producing a significant vagal afferent response yielded an even greater response when administ ered in combination with both subthreshold and suprathreshold doses of CCK. These data demonstrate that, in rats, signals produced by combin ed gastric load and exogenous CCK administration are integrated periph erally and interact synergistically. These results suggest that signal s arising from the vagus may provide sufficient information for the sy nergistic inhibition of food intake produced by combinations of gastri c loads and exogenous CCK.