Differential effects of morphine withdrawal on cerebral beta 1- and beta 2-adrenergic receptors.

Effect of morphine dependence and its withdrawal on the 3H-dihydroalprenolol (3H-DHA) binding for beta -adrenergic receptors, beta 1 and beta 2, was examined by a computerized analysis of biphasic Hofstee plots. The relative density of beta 1 and beta 2 receptors in the rat cerebral cortex was found to be approximately 70% and 30%, respectively. In rats rendered dependent on morphine by a subcutaneous implantation of a morphine pellet, the 3H-DHA binding to beta 1 and beta 2 receptors was not altered. During the stage of withdrawal induced by administration of naloxone, however, the 3H-DHA binding to the cerebral particulate fractions was increased, and this increase was due to the increased binding sites in beta 1 and beta 2 receptors. On the other hand, the apparent affinities of beta and beta 2 for atenolol and salbutamol, selective antagonists for beta 1- and beta 2-adrenergic receptors, respectively, were not altered under these experimental conditions. These results suggest that an abrupt increase in cerebral beta 1-receptor binding sites occurs at morphine withdrawal, and the occurrence of such a super-sensitivity in cerebral beta 1 receptor may be involved in the exhibition and/or maintenance of the abstinence syndrome in morphine-dependent subjects.