Multiple opiate receptors of brain and spinal cord in opiate addiction.
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. Opiates produce their effects by acting on three types of opiate receptors, namely mu, delta and kappa. The qualitative and quantitative aspects of the tolerance-dependence and abstinence symptoms observed after chronic administration of agonists acting at mu-, delta- and kappa-opiate receptors appear to differ. 3. Tolerance-dependence on mu-opiate agonists, such as morphine, is associated with down-regulation of mu-opiate receptors in spinal cord and specific areas of the brain but delta- and kappa-opiate receptors are unchanged. During abstinence from mu-opiate agonists, brain and spinal cord mu-, delta- and kappa-opiate receptors are unaffected. 4. Chronic administration of kappa-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 delta and kappa opiate receptors in brain and spinal cord, but also primarily with a down-regulation of kappa-opiate receptors in spinal cord and specific brain regions. mu-Opiate receptors are unaffected. 5. Chronic administration of delta-opiate agonists results in down-regulation of brain delta-opiate receptors. 6. It is concluded that tolerance-dependence on mu-, delta- and kappa-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Bhargava
H N
HN
Department of Pharmacodynamics (M/C 865), University of Illinois, Chicago 60612.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001923:Brain Chemistry / Q000502:physiology*; D006801:Humans; D009293:Opioid-Related Disorders / Q000378:metabolism*; D011957:Receptors, Opioid / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism*
D001549:Benzamides; D011957:Receptors, Opioid; C045316:cinitapride