Narcotic Receptor Sites in Morphine-dependent Rats

Abstract

THE biochemical basis of the development of tolerance for and dependence on narcotic analgesics has been the subject of much speculation and experiment^1–6. Theories which try to account for these closely related^4,7 phenomena can be grouped into three main classes: (1) the body reacts to narcotic drugs by increasing the rate at which they are destroyed or neutralised (by antibodies, for example) so that a smaller proportion of the total dose reaches the brain receptors²; (2) processes which are directly affected by the narcotic analgesics are circumvented or otherwise accommodated through an indirect physiological adaptation⁶; (3) a direct adaptation takes place in which the number of receptor sites for the narcotics is greatly increased, or their affinities greatly reduced so that large amounts of drugs are needed to fill the available sites and thus effect a response⁵. We wish to present data which effectively rule out this third possibility as a major factor in narcotic drug dependence and tolerance. We show that neither the number, nor the binding affinity, nor the specificity of narcotic receptor sites^8–10 is changed in the morphine-dependent (and therefore also tolerant⁷) rat brain when compared with that of the normal animal.