Abstract-We determined cardiovascular and neurohormonal responses to intracerebroventricular administration of human cocaine-and amphetamine-regulated transcript (CART) peptide 55᎑102 in conscious rabbits. Intracerebroventricular injection of CART 55᎑102 elicited dose-related increases in mean arterial pressure and renal sympathetic nerve activity. Key Words: peptides Ⅲ catecholamines Ⅲ central nervous system Ⅲ glucose Ⅲ renal sympathetic nerve activity A ppetite and feeding behavior are regulated by many neuropeptides, such as neuropeptide Y, corticotrophinreleasing factor, ␣-melanocyte stimulating hormone, and melanin-concentrating hormone. 1,2 Cocaine-and amphetamine-regulated transcript (CART) was originally described as mRNA induced in rat striatum after acute administration of cocaine or amphetamine. 3 At least 6 CART proteins and peptides have been identified in rodents and humans, and some have been purified and sequenced. 4,5 CART peptides have been found in brain areas known to be involved in physiological control of feeding behavior. 4,5 Moreover, intracerebroventricular (ICV) administration of CART peptide fragment 55᎑86, other fragments (54᎑102, 55᎑102, 61᎑102, and 62᎑102), and recombinant CART peptide 55᎑102 cause dose-dependent inhibition of food intake in mice or rats, 6,7 which suggests that these peptides participate in regulation of food intake and feeding behaviors. Amino acid sequences of CART peptides in rat and human are similar, and 95% identity exists between them. 4,5 In the C-terminal region of peptide (55᎑102), a difference of only 1 amino acid exists: a Val3 Ile substitution at position 55. 4,5 CART-immunoreactive cells have been shown to be present not only in hypothalamic nuclei, but also in the medulla, particularly in the nucleus of the solitary tract and area postrema 8 ; these regions of the medulla constitute one of the most important cardiovascular centers of the brain. In addition, ICV administration of CART has been shown to cause increases in plasma corticosterone, oxytocin, and glucose concentrations. 9 We anticipated that CART peptides would be found to participate in cardiovascular and neuroendocrine regulations in addition to feeding behavior in the brain, and we hypothesized that central administration of CART peptides would modulate the hypothalamic-pituitary adrenal axis and change arterial pressure. Accordingly, the present study was designed to investigate the central effects of CART peptides on blood pressure, sympathetic nervous system, and blood variables, including plasma catecholamines, vasopressin, insulin, cortisol, and glucose concentrations. Experiments were conducted in conscious rabbits and included a direct recording of renal sympathetic nerve activity (RSNA), because sympathetic nerve activity or the baroreceptor reflex is strongly influenced by anesthesia. 10,11