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 bodyweight) and the mu-opioid receptor agonist etonitazene (30 microg/kg bodyweight) on the activities of the iodothyronine deiodinase isoenzymes were investigated in nine regions of the rat brain. The experiments were 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 administration of the respective drugs. Interest was focused on changes in the two enzymes that catalyze 1) 5'-deiodination of thyroxine (T4) to the biologically active triiodothyronine (T3), i.e. type II 5'-deiodinase (5'D-II) and 2) 5 (or inner-ring) deiodination of T3 to the biologically inactive 3'3-T2, i.e. type III deiodinase (5D-III). 120 min after administration of ethanol and etonitazene 5D-III activity was selectively 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 the frontal cortex, amygdala and limbic forebrain, and after administration of ethanol in the amygdala alone. These effects on 5'D-II activity were seen at 2100 hours only. In conclusion, the two different addictive drugs both reduced the inactivation of the physiologically active thyroid hormone T3 and enhanced its production. These effects occurred almost exclusively in the brain regions which were most likely to be involved in the rewarding properties of addictive drugs. As thyroid hormones have stimulating and mood-elevating properties, an involvement of these hormones in the reinforcing effects of addictive drugs seems conceivable.
Baumgartner
A
A
Department of Nuclear Medicine (Radiochemistry), Klinikum Benjamin Franklin, Free University of Berlin, Germany.
Pinna
G
G
Hiedra
L
L
Bauer
F
F
Wolf
J
J
Eravci
M
M
Prengel
H
H
Brödel
O
O
Schmidt
G
G
Meinhold
H
H
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D007453:Iodide Peroxidase / Q000378:metabolism*; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000502:physiology; D013963:Thyroid Hormones / Q000378:metabolism*
D001562:Benzimidazoles; D002492:Central Nervous System Depressants; D009294:Narcotics; D017450:Receptors, Opioid, mu; D013963:Thyroid Hormones; D000431:Ethanol; C084835:etonitazene; D007453:Iodide Peroxidase