The dorsal vagal complex as a site for cocaine- and amphetamine-regulated transcript peptide to suppress gastric emptying.

Cocaine- and amphetamine-regulated transcript-derived peptides (CARTp) and corticotropin-releasing factor (CRF) alter feeding and gastrointestinal function after central administration, and the gastric inhibitory effects are mediated through CRF. We hypothesized that dorsal hindbrain effects of CARTp on gastric emptying are mediated by the vagus nerve and that the dorsal vagal complex (DVC) is a site of action for the gastric inhibitory effects of both CARTp and CRF. Rats were equipped with chronic intragastric fistulas and guide cannulas aimed at the fourth ventricle or the DVC. Fourth intracerebroventricular CARTp-induced suppression of 12 ml glucose (12.5%) gastric emptying during fill was blocked by subdiaphragmatic vagotomy. To establish whether the DVC may be a site of action for CARTp and/or CRF, intraparenchymal microinjections (0.25 microl) of CARTp (0.1 and 0.5 microg) and CRF (5 and 10 pmol) were administered in the DVC. Each dose, previously shown to be ineffective after fourth intracerebroventricular administration, suppressed gastric emptying during gastric fill vs. vehicle, but neither peptide changed gastric secretion volume or gastric acidity. The results indicate that the DVC is a target site for CRF and CARTp to inhibit gastric emptying and that the vagus mediates dorsal hindbrain effects of CARTp on gastric motor function.