Time course of short-term and long-term orexigenic effects of Agouti-related protein (86-132)

Agouti-related protein (AGRP) is a newly identified orexigenic peptide that acts as an endogenous antagonist of melanocortin receptors MC3 and MC4. The present study examined the time course of the orexigenic effects of synthetic AGRP (86-132). Intracerebroventricular infusion of 0.1 nmol AGRP (86-132) increased food intake by 450 +/- 81% at 2 h post-injection. A second increase in non-cumulative food intake (512 +/- 135%) was observed at 6 h post-injection. Following a single dose of AGRP (86-132) (0.1 nmol) the increased food intake was sustained for 6 days, occurring in the light cycle of the first 2 days and subsequently switching to the dark cycle of the last 4 days. These time course profiles indicate the complexity of the mechanisms involved in AGRP-induced feeding.