Opioids modulate ingestive behavior, including both feeding and drinking. Extensive studies with selective agonists and antagonists have implicated a number of distinct opioid receptor subtypes. The recent cloning of delta, mu and kappa1 receptors quickly led to the development of antisense techniques which have been used to selectively downregulate mu, delta and kappa1 receptors and their analgesic actions. We now propose to use these anti sense approaches to examine the receptors mediating various aspects of ingestive behavior. Initial studies will examine all three clones, as well as an additional opioid receptor clone which has been reported to encode a kappa3-related receptor. We then will focus our attentions upon mu receptors, using recent studies suggesting the presence of multiple alternatively spliced variants of MOR-1. Finally, we will attempt to localize the anatomical regions mediating the mu receptor actions on feeding.
