EFFECTS OF MORPHINE AND ITS DERIVATIVES ON INTERMEDIARY METABOLISM III. THE INFLUENCE OF CHRONIC MORPHINE POISONING ON THE OXYGEN CONSUMPTION OF RAT SKELETAL MUSCLE

¹ From the Department of Pharmacology, University of Wisconsin, Madison

The rate of oxygen consumption of minced skeletal muscle from normal rats has been determined and compared with similar data from chronically morphinized rats sacrificed at 24 hour intervals during the first week of withdrawal.

The mean Q_OO2 of chronically morphinized muscle from 56 animals calculated without regard to time of withdrawal was 61 per cent greater than the corresponding value for 44 normal rats. The rate of oxygen consumption was greater than normal even one hour after the last dose of morphine and increased rapidly during the first forty-eight hours until at this period it was double the normal level. This high rate persisted until the 96th hour, then gradually subsided but remained above the normal mean at the sixth day. A curve representing these levels of oxygen utilization during the first week of withdrawal parallels almost exactly in its time relationships one representing the intensity of the abstinence syndrome.

The addition of morphine produced an increase in oxygen uptake which was the same in chronically morphinized as in normal muscle regardless of the existing level of metabolism.

Azide, in a concentration which has no significant effect on normal muscle, abolished the increment in oxygen uptake which results from chronic morphine poisoning.

Since malonate produced the same percentage inhibition in chronically morphinized as in normal muscle, irrespective of the level of oxygen consumption, it appears as if the malonate-sensitive fraction of respiration is affected quantitatively rather than qualitatively by chronic morphine poisoning.