Actions of cocaine- and amphetamine-regulated transcript (CART) peptide on regulation of appetite and hypothalamo–pituitary axes in vitro and in vivo in male rats

• Published in: Brain research 2001-03, Vol.893 (1), p.186-194
• Main Authors: Stanley, S.A., Small, C.J., Murphy, K.G., Rayes, E., Abbott, C.R., Seal, L.J., Morgan, D.G.A., Sunter, D., Dakin, C.L., Kim, M.S., Hunter, R., Kuhar, M., Ghatei, M.A., Bloom, S.R.
• Format: Article
• Language: English
• Subjects: Adrenocorticotrophic hormone; Animals; Appetite Regulation - drug effects; Biological and medical sciences; Cocaine- and Amphetamine-regulated transcript; Corticotropin-Releasing Hormone - metabolism; Feeding; Fundamental and applied biological sciences. Psychology; Glucose - administration & dosage; Hormones and neuropeptides. Regulation; Hypothalamo-Hypophyseal System - drug effects; Hypothalamus; Hypothalamus - drug effects; Hypothalamus - metabolism; Hypothalamus. Hypophysis. Epiphysis. Urophysis; In Vitro Techniques; Injections, Intraventricular; Male; Microinjections; Nerve Tissue Proteins - administration & dosage; Nerve Tissue Proteins - metabolism; Neurons - drug effects; Neurons - metabolism; Neuropeptide Y - metabolism; Neuropeptides - metabolism; Paraventricular Hypothalamic Nucleus - cytology; Paraventricular Hypothalamic Nucleus - drug effects; Paraventricular Hypothalamic Nucleus - metabolism; Peptide Fragments - administration & dosage; Pituitary Hormones - blood; Rats; Rats, Wistar; Recombinant Proteins - administration & dosage; Specific Pathogen-Free Organisms; Thyrotropin-Releasing Hormone - metabolism; Vertebrates: endocrinology
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(00)03312-6

Cocaine- and amphetamine-regulated transcript (CART) and CART peptide are abundant in hypothalamic nuclei controlling anterior pituitary function. Intracerebroventricular (ICV) injection of CART peptide results in neuronal activation in the paraventricular nucleus (PVN), rich in corticotrophin-releasing factor (CRH) and thyrotrophin-releasing factor (TRH) immunoreactive neurons. The aims of this study were three-fold. Firstly, to examine the effects of CART peptide on hypothalamic releasing factors in vitro, secondly, to examine the effect of ICV injection of CART peptide on plasma pituitary hormones and finally to examine the effect of PVN injection of CART peptide on food intake and circulating pituitary hormones. CART(55–102) (100 nM) peptide significantly stimulated the release of CRH, TRH and neuropeptide Y from hypothalamic explants but significantly reduced alpha melanocyte stimulating hormone release in vitro. Following ICV injection of 0.2 nmol CART(55–102), a dose which significantly reduces food intake, plasma prolactin (PRL), growth hormone (GH) and adrenocorticotrophin hormone (ACTH) and corticosterone increased significantly. Following PVN injection of CART(55–102), food intake was significantly reduced only at 0.2 and 0.6 nmol. However, PVN injection of 0.02 nmol CART(55–102) produced a significant increase in plasma ACTH. ICV injection of CART peptide significantly reduces food intake. Unlike many anorexigenic peptides, there is no increased sensitivity to PVN injection of CART(55–102). In contrast, both ICV and PVN injection of CART(55–102) significantly increased plasma ACTH and release of hypothalamic CRH is significantly increased by CART peptide in vitro. This suggests that CART peptide may play a role in the control of pituitary function and in particular the hypothalamo–pituitary adrenal axis.