Enhanced oxidative phosphorylation in rat liver mitochondria following prolonged in vivo treatment with imipramine.

1. Effects of prolonged in vivo administration of the tricyclic antidepressant drug imipramine on oxidative energy metabolism in rat liver mitochondria were examined. 2. Imipramine treatment resulted in an increase in state 3 respiration rates with all the substrates tested as early as one week after treatment; this was sustained through the second week of treatment. 3. The changes in respiration rates were accompanied by a selective increase in the intramitochondrial cytochrome aa3 and c + c1 contents after both one and two weeks of treatment. 4. Administration of imipramine did not alter the total liver protein content per g tissue, the mitochondrial protein content per g tissue or the mitochondrial yield. 5. Kinetic analyses of succinoxidase activity in terms of Arrhenius plots indicated possible alterations in mitochondrial membrane lipid milieu and membrane fluidity after the drug treatment, especially in the second week.