title: The effects of acute and repeated administration of T3 to mice on 5-HT1 and 5-HT2 function in the brain and its influence on the actions of repeated electroconvulsive shock.
abstract: The effects of the administration of L-triiodothyronine (T3) On the function of 5-HT in the CNS and its influence on the actions of electroconvulsive shock have been examined in mice. A single injection of T3 (100 micrograms/kg) had no effect 24 hr later on either 5-HT1A-mediated hypothermia, induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.5 mg/kg) or the 5-HT1B-mediated locomotor response to 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl) 1-H-indole (RU 24969; 50 ng i.c.v.). This treatment increased 5-HT2-induced head-twitches, produced by 5-methoxy-N,N'-dimethyltryptamine (5-MeODMT; 2 mg/kg), but did not alter 5-HT2 receptors in the frontal cortex, suggesting that this potentiation was mediated indirectly through a modulatory neurotransmitter. One injection of T3 had no effect on the concentration of 5-HT in the forebrain or mid/hindbrain, but increased 5-HIAA in the latter region. Daily injections of T3 for 10 days attenuated the responses to both 8-OH-DPAT and RU 24969. Furthermore, 5-MeODMT-induced head-twitches returned to control values and this was accompanied by a 10% decrease in 5-HT2 receptors in the cortex. Repeated administration of T3 increased levels of 5-HT in mid/hindbrain and concentrations of 5-HIAA both here and in forebrain. Hence, treatment with T3 attenuated the function of 5-HT1A and 5-HT1B receptors, but increased 5-HT2-mediated responses, although the time-courses for these effects were different. Triiodothyronine also enhanced the synthesis and turnover of 5-HT in the brain of the mouse. Repeated electroconvulsive shock (90 V, 1 sec) decreased the hypothermia induced by 8-OH-DPAT. However, 5-MeODMT-induced head-twitches were enhanced by acute and repeated electroconvulsive shock. Administration of T3 together with electroconvulsive shock did not alter the effects of electroconvulsive shock on 5-HT1A-mediated hypothermia, but markedly potentiated its actions on 5-HT2-mediated responses. These findings provide possible pharmacological evidence for the suggested antidepressant effects of T3 and the potentiation of antidepressant therapy by this thyroid hormone.
authors.affiliation: MRC Unit, Radcliffe Infirmary, Oxford, U.K.
authors.forename: D J
authors.initials: DJ
authors.lastname: Heal
authors.forename: S L
authors.initials: SL
authors.lastname: Smith
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D004597:Electroshock; D007035:Hypothermia / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014284:Triiodothyronine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D007211:Indoles; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D014284:Triiodothyronine; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin