EFFECTS OF MORPHINE AND ITS DERIVATIVES ON INTERMEDIARY METABOLISM II. THE INFLUENCE OF THIAMIN DEFICIENCY ON THE RESPIRATION OF SKELETAL MUSCLE AND COCARBOXYLASE CONTENT OF TISSUES OF NORMAL AND CHRONICALLY MORPHINIZED RATS

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

Severe thiamin deficiency was induced concurrently with chronic morphine poisoning in albino rats. Although the animals in this group exhibited footgnawing and succumbed earlier than the thiamin-deficient controls, no increase in the pre-injection irritability was obtained, either in this group or in the control groups, by the objective struggle method.

The addition of either morphine or pyruvate results in a marked increase in the no-substrate oxygen uptake of normal rat skeletal muscle. When both are added together, the resultant increase is greater than that which would be expected from summation of the two individual effects.

The extra oxygen uptake resulting from the addition of pyruvate to chronically morphinized rat skeletal muscle is less than half of that which occurs in normal muscle, and the synergistic increase noted in normal muscle when morphine and pyruvate are added is lacking. Results of a similar and even more striking nature were obtained with thiamin-deficient muscle.

The increase in the oxygen uptake of normal muscle resulting from the addition of cocarboxylase in the presence of added pyruvate was entirely lacking in both thiamin-deficient and chronically morphinized muscle.

The cocarboxylase content of brain, liver and skeletal muscle is not changed significantly by chronic poisoning with morphine, codeine or phenobarbital. Neither does the chronic administration of morphine modify significantly the degree of reduction of cocarboxylase induced by thiamin deficiency.