Regulations of opioid dependence by opioid receptor types

Three major types of opioid receptors. designated mu, delta, and kappa, are widely expressed in the CNS, Development of selective receptor ligands and recent cloning of each receptor have contributed greatly to our increasing knowledge of the neuropharmacological profile of each opioid receptor type . It is of interest to note that they include noncompetitive and allosteric interactions among their types. This review focuses on the functional inte raction among these opioid receptor types that contribute to opioid depende nce. Various studies provide arguments to support substantial roles for mu -opioid receptors and the possible involvement of delta -opioid receptors i n the development of physical and psychological dependence on morphine, Nor adrenergic transmission originating in the locus coeruleus is most likely t o play the primary causal role in the expression of physical dependence on morphine. Tn contrast, many studies have pointed to the mesolimbic dopamine rgic pathway projecting from the ventral tegmental area to the nucleus accu mbens as a critical site for the initiation of psychological dependence on opioids. It is noteworthy as the broad existence of opposing interactions b etween mu/delta- and kappa -receptors in the brain. The activation of kappa -receptors leads to the suppression of unpleasant mu/delta -mediated side effects such as the rewarding effect. Considering the functional interactio n among opioid receptor types, the co-administration of morphine-like compo unds with kappa -receptor agonists may constitute a preferable and superior approach to the treatment of pain with fewer side effects. (C) 2001 Elsevi er Science Inc. All rights reserved.