It has been reported that reactive oxygen species in the hypothalamus is involved in regulating appetite and that hypothalamic neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART) participate in amphetamine (AMPH)-induced appetite suppression. This study examined whether the endogenous anti-oxidative enzyme superoxide dismutase (SOD) was involved in CART-mediated appetite control in AMPH-treated rats. The rats were treated with AMPH for one day, and changes in feeding behavior and expression levels of hypothalamic NPY, CART, and SOD were assessed and compared. The results showed that food intake and NPY decreased during AMPH treatment, whereas CART and SOD increased. Moreover, an intracerebroventricular infusion of NPY antisense oligonucleotide before daily AMPH treatment enhanced the decreases in food intake, body weight, and NPY expression and the increases in CART and SOD expression. The results suggest that hypothalamic SOD participates in regulating NPY- and CART-mediated appetite control during AMPH treatment. These results may advance the knowledge of the molecular mechanism of AMPH-evoked appetite suppression.
