Multiple opiate receptors of brain and spinal cord in opiate addiction

Abstract

1. 1. Chronic administration of opiates to rodents results in the development of tolerance to their pharmacological effects. Physical dependence also develops and is shown by the appearance of abstinence syndrome. 2. 2. Opiates produce their effects by acting on three types of opiate receptors, namely μ, δ and κ. The qualitative and quantitative aspects of the tolerance-dependence and abstinence symptoms observed after chronic administration of agonists acting at μ-, δ- and κ-opiate receptors appear to differ. 3. 3. Tolerance-dependence on μ-opiate agonists, such as morphine, is associated with down-regulation of μ-opiate receptors in spinal cord and specific areas of the brain but δ- and κ-opiate receptors are unchanged. During abstinence from μ-opiate agonists, brain and spinal cord μ-, δ- and κ-opiate receptors are unaffected. 4. 4. Chronic administration of κ-opiate agonists, such as U-50,488H, results in the development of tolerance to its pharmacological effects and a mild degree of physical dependence. Such changes are associated not only with alterations of δ and κ opiate receptors in brain and spinal cord, but also primarily with a down-regulation of κ-opiate receptors in spinal cord and specific brain regions. μ-Opiate receptors are unaffected. 5. 5. Chronic administration of δ-opiate agonists results in down-regulation of brain δ-opiate receptors. 6. 6. It is concluded that tolerance-dependence on μ-, δ- and κ-opiate receptors is associated with down-regulation of their own type of receptors in the spinal and supraspinal areas. Abstinence, on the other hand, does not alter brain and spinal cord opiate receptors. However, changes in opiate receptors in tolerance-dependence development may not be sufficient to explain the mechanism involved in such processes and may perhaps involve, in addition, other neurotransmitter receptor systems.