Effects of tranylcypromine on thyroid hormone metabolism and concentrations in rat brain

The effect of 14 days administration of the anti-depressant tranylcypromine (TCP) on iodothyronine deiodinase activities and the concentrations of thyroxine (T4) and triiodothyronine (T3) were investigated in homogenates of up to nine regions of the rat brain. The activity of the 5III deiodinase isoenzyme, which catalyses the inactivation of T3 to 3,3'-diiodothyronine (3,3'-T2), was enhanced in eight brain regions. However, the brain levels of T4 were completely unchanged and the T3 concentrations were significantly reduced in the frontal cortex only. Therefore, we also measured the T3 concentrations of three subcellular fractions (nuclei, synaptosomes and mitochondria) of six brain regions. TCP induced a significant reduction in T3 levels in the synaptosomes of the frontal cortex and significant increases in the mitochondrial T3 concentrations in the amygdala. The latter effect was replicated after 14 days administration of 5 mg/kg desipramine. No effects of either drug on nuclear concentrations of T3 were seen in any brain region. As the amygdala is critically involved in the affective coloring of sensory stimuli, the increase in T3 concentrations in the mitochondria of this brain region may be of relevance for the mechanism of action of anti-depressant drugs.