Knocking down PAC1Rs in the VMN increases daily food intake and cumulative body weight change. Knocking down VMN PAC1Rs increased daily food intake by day 12 (A) and increased body weight by day 18 (B). Inset in A shows a significant increase in dark phase food take but not light phase feeding averaged over the 21-day period. Knocking down VMN PAC1Rs is sufficient to block PACAP-induced decreases in food intake (C) and body weight (D). Data are expressed as means ± SE, *P < 0.05 compared with control (n = 8 rats/group). NSc, nonsilencing control; PAC1R, pituitary adenylate cyclase receptor; PACAP, pituitary adenylate cyclase-activating polypeptide; VMN, ventromedial nuclei.