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Ribonuclease has been studied in the whole brain homogenate of mice after a single dose of morphine (10 mg/kg), during the development of tolerance and dependence, during the course of withdrawal and naloxone administration. The enzyme increased dose dependently following the administration of morphine. Withdrawal caused a sudden fall in the enzyme with partial recovery by the 6th day of abstinence. Naloxone injections in normal, tolerant, dependent and deprived animals caused a reduction in the enzyme level. The morphine-induced increase in enzyme activity is suggested to be in direct correlation with a reduction in protein synthesis which can be ascribed to a disturbance of the translation processes.

The possible role of succinic dehydrogenase (SD) in producing physical dependence to morphine by affecting tissue respiration was investigated in Swiss albino mice during the development of morphine tolerance through a period of addiction and naloxone withdrawal therapy. Tolerance and physical dependence were induced by injecting the mice with morphine sulfate subcutaneously at 8-hour intervals, increasing the dose from 10 mg/kg BW every 24 h for 15 days. The animals were considered to be addicted when they were able to tolerate an otherwise lethal dose of 150 mg/kg 3 times a day. Results indicated that succinic dehydrogenase was inhibited throughout the 15-day period of morphine administration and that this effect was greatest in tolerant animals. Increasing the dose and duration of treatment did not cause further decreases in enzyme activity; instead, after 15 days levels of enzyme activity increased in addicted animals compared with tolerant mice. Furthermore, morphine abstinence for 2 days, markedly increased the levels of SD activity, while 6 days of abstinence had little effect. Naloxone withdrawal at each stage was associated with increased SD activity, but the increase was significant only in tolerant mice.