THE INFLUENCE OF DESIPRAMINE ON THYROID-HORMONE METABOLISM IN RAT-BRAIN

The effect of the antidepressant desipramine (DMI) on the activities o f the three iodothyronine deiodinase isoenzymes involved in the centra l metabolism of thyroid hormones were investigated in 11 brain regions and 3 peripheral tissues in the rat. The investigations were carried out at three different times during the light/dark cycle: 5 A.M., 1 P. M. and 11 P.M. interest is focused on changes in the two enzymes that catalyze: i) the 5'deiodination of T-4 to the biologically active T-3, i.e., type II 5'deiodinase (5'D-II), and ii) the 5 (or inner-ring) de iodination of T-3 to the biologically inactive 3,3'T2, i.e., type III 5 deiodinase (5D-III). Fourteen days' treatment with 20 mg/kg DMI, but not with 5 mg/kg DMI, induced significant increases in 5'D-II in eigh t different areas of the CNS. The regions affected were identical to t hose that receive noradrenergic input from the locus coeruleus. Even c ontrol animals showed a circadian rhythm of 5'D-II activity in some br ain regions, and the effects of DMI also depended on the time of death within the 24-hr rhythm. 5D-III was not affected. Serum T-4 were lowe r after administration of DMI, most probably because of enhanced tissu e uptake of T-4. This is in line with the corresponding finding in dep ressed patients, indicating that similar changes in both central and p eripheral thyroid hormone metabolism may occur after antidepressant ph armacotherapy in both humans and rats. These data support the hypothes is that interactions with the CNS metabolism of the thyroid hormones m ay be involved in the mechanisms of action of DMI.