Submitted on April 7, 2004
Accepted on January 17, 2006
The dorsal vagal complex as a site for cocaine- and amphetamine-regulated transcript peptide to suppress gastric emptying
Ulrika Smedh1* and Timothy H Moran2
1 Department of Surgery, Lund University Hospital, Lund, Sweden
2 Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
* To whom correspondence should be addressed. E-mail: ulrika.smedh{at}med.lu.se.
Cocaine- and amphetamine-regulated transcript-derived peptides (CARTp) and corticotropin-releasing factor (CRF) alter feeding and gastrointestinal function following central administration and the gastric inhibitory effects are mediated through corticotropin-releasing factor. 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 i.c.v. CARTp-induced suppression of 12 ml glucose (12.5%) gastric emptying during fill was blocked by subdiaphragmatic vagotomy. To establish whether the dorsal vagal complex may be a site of action for CARTp and/or CRF, intraparenchymal microinjections (0.25 µl) of CARTp (0.1 and 0.5 µg), and CRF (5 pmol and 10 pmol) were administered into the DVC. Each dose, previously shown to be ineffective after 4th i.c.v. 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.
