Actions of cocaine- and amphetamine-regulated transcript (CART) peptide onregulation of appetite and hypothalamo-pituitary axes in vitro and in vivoin male rats

Cocaine- and amphetamine-regulated transcript (CART) and CART peptide are a bundant in hypothalamic nuclei controlling anterior pituitary function. Int racerebroventricular (ICV) injection of CART peptide results in neuronal ac tivation in the paraventricular nucleus (PVN), rich in corticotrophin-relea sing factor (CRH) and thyrotrophin-releasing factor (TRH) immunoreactive ne urons. The aims of this study were three-fold. Firstly, to examine the effe cts of CART peptide on hypothalamic releasing factors in vitro, secondly, t o examine the effect of ICV injection of CART peptide on plasma pituitary h ormones and finally to examine the effect of PVN injection of CART peptide on food intake and circulating pituitary hormones. CART(55-102) (100 nM) pe ptide significantly stimulated the release of CRH, TRH and neuropeptide Y f rom hypothalamic explants but significantly reduced alpha melanocyte stimul ating hormone release in vitro. Following ICV injection of 0.2 nmol CART(55 -102), a dose which significantly reduces food intake, plasma prolactin (PR L), growth hormone (GH) and adrenocorticotrophin hormone (ACTH) and cortico sterone increased significantly. Following PVN injection of CART(55-102), f ood 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 pla sma 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 CR H is significantly increased by CART peptide in vitro. This suggests that C ART peptide may play a role in the control of pituitary function and in par ticular the hypothalamo-pituitary adrenal axis. (C) 2001 Elsevier Science B .V. All rights reserved.