Interaction between orexins and the mesolimbic system for overriding satiety

In North American society, it is all too common for the intake of calories to outweigh an individual's energy demands. Such over-consumption where high-energy foods are readily available undoubtedly contributes to the growing problem of obesity. Palatable food stimulates brain circuits similar to those that mediate behavioral responses to drugs of abuse, which may underlie the continuation of food intake long after energy requirements are met. Among the brain areas implicated in reward and food intake, the lateral hypothalamus (LH) has long been recognized as a common region involved in both. It has been suggested that orexin neurons that are expressed exclusively within and adjacent to the LH comprise a major cellular substrate for the functioning of the LH. Here, we review the idea that the orexin neuropeptides play a key role in the rewarding aspects of food intake through interactions with both peripheral and central signals reflecting current energy stores as well as the classic reward pathway--the mesolimbic dopamine system. Furthermore, a possible heterogeneity of orexin neurons is discussed. Uncovering orexin's role in food reinforcement may provide insight into hyperphagia and obesity. In addition, the idea that food intake and substance abuse involve similar brain circuitry suggests potential for a single treatment aiding both obesity and addiction.