CART in the dorsal vagal complex: sources of immunoreactivity and effects on Fos expression and food intake

Abstract

CART-peptide (CARTp) has been shown to suppress food intake, particularly when injected into the 4th ventricle of rats, and the presence of CART in nodose ganglia suggested a role in satiation. Based on retrograde tracing from the DVC combined with CART immunohistochemistry and supranodose vagotomy, we found that CART immunoreactivity in varicose fibers of the dorsal vagal complex originates from vagal afferents, sparse projections from the medullary reticular formation and the arcuate/retrochiasmatic nucleus of the hypothalamus, and most likely also from local CART neurons in the area postrema and NTS. In the nodose ganglia, 17% of neurons with projections to the stomach and 41% to the duodenum express CART-IR. CART-IR vagal afferents significantly contribute to the rich fiber plexus in mainly the commissural NTS and the adjacent area postrema. Injections of CARTp into the 4th ventricle strongly suppressed sucrose drinking and stimulated expression of c-Fos in the NTS. Injections of CARTp directly into various subnuclei of the NTS were less effective in suppressing food intake. The findings suggest that the critical site for CART's suppression of food intake is not in the termination zone of CART-containing vagal afferents in the commissural NTS, and that CART release from vagal afferent terminals plays a minor role in satiation. The functional role of CART in vagal afferents and the site of food intake suppression by 4th ventricular CARTp remain to be determined.