EFFECTS OF ACUTE ADMINISTRATION OF ETHANOL AND THE MU-OPIATE AGONIST ETONITAZENE ON THYROID-HORMONE METABOLISM IN RAT-BRAIN

The effects of acute, low-dose administration of ethanol (1 g/kg bodyw eight) and the mu-opioid receptor agonist etonitazene (30 mu g/kg body weight) on the activities of the iodothyronine deiodinase isoenzymes w ere investigated in nine regions of the rat brain. The experiments wer e performed at three different times of the 24-h cycle (1300, 2100 and 0500 hours) and the rats were decapitated 30 and 120 min after admini stration of the respective drugs. Interest was focused on changes in t he two enzymes that catalyze 1) 5'-deiodination of thyroxine (T-4) to the biologically active triiodothyronine (T-3), i.e. type II 5'-deiodi nase (5'D-II) and 2) 5 (or inner-ring) deiodination of T-3 to the biol ogically inactive 3'3-T-2, i.e. type III deiodinase (SD-III). 120 min after administration of ethanol and etonitazene SD-III activity was se lectively inhibited in the frontal cortex (at 1300 and 1700 hours) and the amygdala (at all three measuring times). The 5'D-II activity was significantly enhanced 30 min after administration of etonitazene in t he frontal cortex, amygdala and limbic forebrain, and after administra tion of ethanol in the amygdala alone. These effects on 5'D-II activit y were seen at 2100 hours only. In conclusion, the two different addic tive drugs both reduced the inactivation of the physiologically active thyroid hormone T-3 and enhanced its production. These effects occurr ed almost exclusively in the brain regions which were most likely to b e involved in the rewarding properties of addictive drugs. As thyroid hormones have stimulating and mood-elevating properties, an involvemen t of these hormones in the reinforcing effects of addictive drugs seem s conceivable.