Peptides that regulate food intake - Separable mechanisms for dorsal hindbrain CART peptide to inhibit gastric emptying and food intake

摘要

We investigated whether dorsal hindbrain and/or peripheral cocaine- and amphetamine-regulated transcript peptide (CARTp) acts to suppress gastric emptying of a caloric stimulus. Furthermore, effects of dorsal hindbrain CARTp on sucrose consumption and licking microstructure was studied, as well as the possible contribution of corticotropin-releasing factor (CRF) receptors to mediate effects of CARTp downstream on emptying and sucrose intake. Rats bearing gastric fistulas received intragastric infusions (1.0 ml/min) of 12 ml 12.5% glucose. Gastric samples were withdrawn immediately after the intragastric infusion to reflect emptying during gastric fill. CARTp injected in the fourth ventricle intracerebroventricularly (0.5 and 1.0 mug) suppressed gastric emptying. CARTp reduced sucrose intake at similar doses and altered a variety of lick microstructure variables ( no. of licks, bursts, clusters, licks/burst, licks/clusters, interlick interval, first meal size, and first meal duration). Pretreatment with the CRF antagonist alpha-helical CRF-(9- 41) blocked the effect of 1.0 mug CARTp on gastric emptying but not on sucrose consumed or on any of the licking microstructure parameters. These data demonstrate differential mediation of the feeding and gastric inhibitory effects of CARTp and suggest that CARTp-induced inhibition of gastric emptying does not contribute to this peptide's ability to inhibit food intake.