Effect of narcotic dependence and withdrawal on striatal dopamine-sensitive adenylate cyclase and synaptosomal cyclic AMP metabolism.

In rats rendered tolerant to the dependent on morphine, striatal cyclic AMP metabolism was significantly enhanced as reflected by elevated cyclic AMP levels and adenylate cyclase activity. Following withdrawal from morphine treatment, whereas the activity of straital adenylate cyclase was significantly reduced when compared to morphine-dependent rats, the drop in cyclic AMP was not significant. Although addition of dopamine (40 muM) stimulated equally well the striatal adenylate cyclase from control or morphine-dependent animals, the activity of dopamine-stimulated enzyme was blocked in animals undergoing withdrawal. The crude synaptosomal fraction of the whole brain obtained from morphine-dependent rats exhibited an even more pronounced increase in cyclic AMP which was accompanied by elevated adenylate cyclase and protein kinase activity. Naloxone administration suppressed this rise in cyclic AMP and reversed the morphine-stimulated increases in adenylate cyclase and protein kinase. Following the withdrawal of morphine treatment, alterations in cyclic AMP metabolism were similar to those noted for the morphine-naloxone group.