Opioids as agents of reward-related feeding: a consideration of the evidence.

Gerard Smith was one of the pioneers in the field of neuropeptidergic control of food intake. He established methodology and criteria used to determine whether a neuropeptide acts as an endogenous satiety factor. More recently, he theorized that there are direct and indirect controls of meal size. Direct controls include those that depend upon contact of food with preabsorptive receptors from the tip of the tongue to the end of the small intestine, and indirect controls include those that do not depend upon direct contact of mucosal receptors, such as learning and metabolism. In this review, we consider the evidence that opioids are mediators of reward-related feeding. We address these issues adopting Smith's approach to problem solving, including an evaluation of the opioids as controllers of the meal. We also present a novel concept of "hedonic restriction," resulting in a change in opioid gene expression. Overall, we believe the evidence supporting opioid participation in reward-driven and other types of ingestion is very strong, but much work remains before we understand how opioids contribute to the widely distributed neural network that controls ingestive behavior.