Agouti-related protein: appetite or reward?

Agouti-related protein (AgRP) is an orexigenic peptide that acts as an antagonist of the melanocortin-3 and -4 receptors in the hypothalamus. Studies suggest that the melanocortin and opioid systems interact in the control of ingestive behavior. Also, AgRP has been shown to especially increase intake of a palatable diet. Given these observations, we wished to examine whether the effects of AgRP on ingestive behavior resemble those of opioids. AgRP was injected into the hypothalamic paraventricular nucleus in animals given a choice between a palatable sucrose solution and calorically dense chow. As a result of AgRP injection, animals increased intake of chow but not sucrose relative to controls, in contrast to what has been seen with opioid agonists. These results together with prior findings suggest that the primary effect of AgRP is to cause an increase in food intake to satisfy energy needs, though AgRP also has opioid-like effects, possibly due to melanocortin-opioid interactions.