SUBCHRONIC ADMINISTRATION OF FLUOXETINE TO RATS AFFECTS TRIIODOTHYRONINE PRODUCTION AND DEIODINATION IN REGIONS OF THE CORTEX AND IN THE LIMBIC FOREBRAIN

The effects of subchronic administration of the antidepressant fluoxetine (15 mg/kg i.p., 14 days) on thyroid hormone metabolism were investigated in 11 regions of the CNS and three peripheral tissues in the rat. Fluoxetine significantly enhanced the activity of the 5'II-deiodinase isoenzyme (5'D-II), which catalyzes the deiodination of the inactive prohormone thyroxine (T4) to the active compound triiodothyronine (T3) in areas of the cortex, the limbic forebrain and the striatum. The activity of the 5D-III deiodinase isoenzyme (5D-III), which catalyzes the further deiodination of T3 to the inactive metabolite 3,3'-T2, was inhibited in the first two of these areas. The areas affected were roughly the same as those with the highest density of 5-HT2 receptors in rat brain. Theoretically, the enhancement 5'D-II activity, together with a concomitant decrease in 5D-III activity, should lead to a rise in T3 concentrations. Whether or not these effects are involved in the as yet unknown mechanism of action of this antidepressant compound is discussed.