Substance P in the lateral hypothalamic area regulates binge-like eating behaviors in mice.

Binge eating disorder (BED) is the most common type of eating disorder; however, the neural circuit mechanisms underlying BED remain elusive. Here, we report that tachykinin-expressing neurons in the lateral hypothalamic area (LH(Tac1) neurons) are inhibited during binge-like eating behaviors in mice. We identified LH(Tac1) neurons as key mediators of binge-like eating behaviors and reported that the LH(Tac1)→ lateral periaqueductal gray (LPAG) circuit is critical to the regulation of binge-like eating behaviors. Moreover, Substance P (SP) released by LH(Tac1) neurons modulates binge-like eating behaviors by influencing the input of glutamate to LPAG cells, which receive projections from LH(Tac1) neurons. In summary, these findings point to the SP as a key node in BED circuits.