Mouse Brain DNA‐Dependent RNA Polymerases After Chronic Morphine Treatment

Abstract: Chronic morphine pellet implantation was found to decrease the specific activity of two forms of mouse brain RNA polymerase I and to alter the requirements of Mg²⁺ and Mn²⁺ for the activities of RNA polymerases II and III. DNA‐dependent RNA polymerases were partially purified from small dense nuclei isolated from brains of naive and morphine tolerant‐dependent mice, and three RNA polymerases were separated on a DEAE‐Sephadex A‐25 column. The three fractions, referred to as peak I, peak II, and peak III, were studied, characterized, and identified as being RNA polymerases I, II, and III, respectively. Chronic‐morphine pellet implantation resulted in a lower specific activity of RNA polymerase I, but the specific activities of RNA polymerases II and III were not affected. This effect was prevented by preimplantation of a naloxone pellet and thus was narcotic‐specific. Chronic morphine treatment lowered the concentration of Mg²⁺ required for optimal activity of RNA polymerase II and elevated the Mn²⁺‐Mg²⁺ activity ratios of RNA polymerases II and III. A second DEAE‐Sephadex A‐25 column chromatography of the peak I RNA polymerase was carried out, revealing five component activity peaks. Two of these contained lower specific activities as a result of chronic morphine pelletimplantation. These specific changes in RNA polymerase function in morphine tolerance‐dependence may be associated with the elevated chromatin template activities, altered chromatin phosphorylation, and elevated rates of cell‐free translation that have been reported by others.