Hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) are involved in the regulation of amphetamine (AMPH)-induced appetite suppression. The aim of this study was to examine whether hypothalamic cocaine- and amphetamine-regulated transcript (CART) is also involved in the acute anorectic action of AMPH. Rats were treated with AMPH and changes in feeding behavior and expression levels of NPY, POMC, and CART were assessed and compared 24 h later. Results showed that feeding and expression level of NPY decreased, while the expressions of CART (55-102), melanocortin 3 receptor (MC3R), and MC4R increased, following AMPH treatment. To examine the role of NPY in regulating POMC and CART, intracerebroventricular infusion of NPY antisense was applied 60 min prior to AMPH treatment. NPY knockdown led to further decreases in AMPH-induced anorexia and NPY expression and increases in MC4R, MC3R, and CART (55-102) expressions. This indicated that both hypothalamic CART and POMC participate in the regulation of NPY-mediated appetite control during AMPH treatment. The results of this study may advance the knowledge regarding the molecular mechanism of AMPH-induced appetite suppression.
