Studies on the Physical Dependence Liability of Analgesics

Influence of morphine on the fine structure of mitochondria in the cells of zona fasciculata in rat adrenal cortex was studied electronmicroscopically. By the administration of morphine to rats in a dose of 20 mg/kg the specific honeycomb like structure of mitochondria in adrenocortical cells was observed to be transformed from vesicular forms into tubulo-vescicular or tubular ones while the changed structure gradually diminished during repeated administration of the drug. Withdrawal of morphine caused an extensive re-transformation while with a reinjection of the drug a prompt restoration to the pretreated structure was observed. The feasibility of utilizing this transformation as an index of physical dependence liability has been discussed.