Recombinant CART peptide induces c-Fos expression in central areas involved in control of feeding behaviour

We have recently shown that the hypothalamic neuropeptide CART (cocaine-amp hetamine-regulated-transcript) is a leptin dependent endogenous satiety fac tor in the rat. In the present study we confirm and extend our previous obs ervations by showing that intracerebroventricular (i.c.v.) administered CAR T(42-89) dose-dependently inhibits 3-h food intake in food restricted rats with a lowest effective dose of 0.5 mu g. CART also potently inhibits NPY-i nduced food intake in satiated rats as well as nighttime food intake in fre e feeding animals. To identify brain areas potentially involved in mediatin g the anorectic effects of CART, the temporal expression pattern of the imm ediate early gene c-fos was examined in the central nervous system by immun ohistochemistry in rats receiving recombinant CART. Compared to vehicle, CA RT induced c-Fos expression in several hypothalamic and brainstem structure s implicated in the central control of food intake. In the hypothalamus, hi gh numbers of c-Fos immunoreactive (-ir) cells were observed in the medial parvocellular part of the paraventricular nucleus and in the posterior part of the dorsomedial nucleus. Lower numbers of c-Fos positive nuclei were fo und in the supraoptic and arcuate nuclei. A relatively high number of c-Fos -ir cells was found in the central nucleus of the amygdala. In the brainste m, c-Fos-positive nuclei were found in the parabrachial nucleus, and in the nucleus of the solitary tract. Notably both the area postrema and the dors al motor nucleus of the vagus were virtually devoid of c-Fos-ir cells. The present experiments suggest that CART peptide exerts its inhibitory effects on appetite by activating hypothalamic and brainstem neurones implicated i n the central control of feeding behaviour and metabolism. (C) 1999 Elsevie r Science B.V. All rights reserved.