title: Fourth ventricular CART peptide induces c-fos in the area postrema and nucleus of the solitary tract via a CRF-receptor dependent mechanism.
abstract: Cocaine-and amphetamine-regulated transcript peptides (CARTp) suppress gastric emptying and nutritional intake following 4th icv administration. Whereas, the CARTp inhibition of gastric emptying was blocked by pre-treatment with a non-selective corticotropin releasing factor (CRF) antagonist, sucrose drinking was not, suggesting that CARTp- and CRF controls for food intake and gastric emptying are operated through separable dorsal hindbrain mechanisms. The aim of the study was to explore CARTp-CRF brainstem interactions on patterns of neuronal activation in areas of the brainstem and midbrain relevant to gastrointestinal control and feeding regulation. Rats received 4th icv injections of combinations of vehicle, CARTp (1μg), or the nonselective CRF antagonist, α-helical CRF9-41 (αCRF), in a randomized order. Brain sections were processed for c-fos by immunohistochemistry followed by image analysis at defined levels of the brain. CARTp (1μg, 4th icv) induced a robust c-fos response in the nucleus of the solitary tract (NTS) and area postrema (AP), whereas, no c-fos could be detected in the parabrachial nucleus (PBN), the paraventricular nucleus of the hypothalamus (PVN) or the arcuate nucleus of the hypothalamus (ARC). The c-fos expression in the structures of the dorsal vagal complex (DVC) was completely blocked by pre-treatment with the CRF antagonist, which did not by itself induce c-fos at any examined level. After CARTp and αCRF in combination, there was a tendency towards an increased c-fos response in the ARC. We conclude that CARTp activates cells of the area postrema and NTS via a downstream, CRF-dependent mechanism.
authors.affiliation: Dept. of Surgery, Institute for Clinical Sciences, Sahlgrenska Academy University of Gothenburg, Göteborg, Sweden. Electronic address: ulrika.smedh@gu.se.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Smedh
authors.affiliation: Dept. of Psychiatry and Behavioral Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Scott
authors.affiliation: Dept. of Psychiatry and Behavioral Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Moran
mesh_terms: D000818:Animals; D031608:Area Postrema / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004435:Eating / Q000502:physiology; D020546:Fourth Ventricle; D041981:Gastrointestinal Tract / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D017552:Solitary Nucleus / Q000378:metabolism*; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D018019:Receptors, Corticotropin-Releasing Hormone; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41)
keywords: Arcuate nucleus; CART; Nucleus of the solitary tract; Parabrachial nucleus; Paraventricular nucleus