NF-κB knockdown can modulate amphetamine-mediated feeding response.

This study determined if transcription factor NF-κB is involved in the effect of amphetamine (AMPH)-mediated feeding response. Moreover, possible roles of hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) were also investigated. AMPH was administered daily to rats for four days. Changes in NF-κB, NPY and POMC expression were assessed and compared. The NPY gene was down-regulated with maximal response on Day 2 during AMPH treatment, which was consistent with the response to feeding behavior. In contrast, NF-κB and POMC genes were up-regulated, and their expression was increased by about 200% and 450%, respectively, with maximal response on Day 2. Moreover, NF-κB DNA binding ability and expression were increased similar to that of POMC. To examine further if NF-κB was involved, intracerebroventricular infusion of NF-κB antisense oligonucleotide was performed 1 h before the daily AMPH dosing in freely moving rats. Results showed that NF-κB knockdown could modify AMPH anorexia as well as NPY and POMC expression. The present findings prove that cerebral NF-κB participates in AMPH-mediated appetite suppression, possibly by modulating NPY and POMC expression. These results may aid in therapeutic research on AMPH and AMPH-like anti-obesity drugs.