THE EFFECTS OF DESIPRAMINE ON THYROID-HORMONE CONCENTRATIONS IN RAT-BRAIN

The effects of the antidepressant desipramine on the tissue concentrat ions of thyroxine and triiodothyronine in 9 different regions of the b rain and also in the pituitary and liver were investigated in male rat s. The investigations were carried out at three different times of the light/dark cycle: 5 a.m., 1 p.m. and 11 p.m. After fourteen days' tre atment with 20 mg/kg/day kg/day desipramine by gavage the concentratio ns of triiodothyronine in the frontal and parieto-occipital cortex wer e significantly higher than in the saline-treated controls, those in t he hippocampus lower and those in the 6 remaining brain regions the sa me. In 8 areas of the brain the concentrations of thyroxine were lower in the desipramine-treated rats and the tissue ratios of triiodothyro nine to thyroxine were enhanced in 6 regions. These effects are most l ikely the result of the action of desipramine on the activity of the i soenzyme 5'II deiodinase. This enzyme catalyzes the deiodination of th yroxine to triiodothyronine in rat brain and its activity has recently been reported to be enhanced by desipramine. The observed effects wer e dose-dependent and also strongly dependent upon the time within the 24 h light/dark cycle at which the hormone concentrations were measure d. No effects of desipramine were seen in the pituitary or liver after 14 days' treatment, or in various areas of the central nervous system 24 h after administration. In view of the psychotropic properties of thyroid hormones, it seems possible that the observed increases in tri iodothyronine concentrations, particularly in cortical areas, are invo lved in the mechanisms of action of desipramine.