Effect of triiodothyronine on antidepressant screening tests in mice and on presynaptic 5-HT 1A receptors: Mediation by thyroid hormone α receptors

T. Lifschytz, P. Zozulinsky, R. Eitan, G. Landshut, S. Ohayon, B. Lerer

Research output: Contribution to journalArticlepeer-review

Abstract

Although triiodothyronine (T3) is widely used clinically, preclinical support for its antidepressant-like effects is limited, and the mechanisms are unknown. We evaluated 1) the antidepressantlike effects of T3 in the novelty suppressed feeding test (NSFT), tail suspension test (TST), and forced swim test (FST), 2) the role of presynaptic 5-HT 1A receptors in the antidepressant-like mechanism of T3 by the hypothermic response to the 5-HT 1A receptor agonist, 8-hydroxy-N,N-dipropyl-2-aminotetralin (8- OH-DPAT), 3) the thyroid hormone receptor type mediating the antidepressant-like effects by concurrent administration of the specific thyroid hormone α receptor (TRα) antagonist, dronedarone, and 4) the presence of these effects in both genders. Male and female BALB/c mice were administered 1) T3 (20, 50, 200, or 500 μg/kg per day) or vehicle or 2) T3 (50 μg/kg per day), dronedarone (100 μM/day), or the combI Nation intraperitoneally for 21 days and then underwent a behavioral test battery. The NSFT showed a shortened latency to feed in males at the two lower T3 doses. The TST and FST showed decreased immobility in male mice at T3 doses >20 μg/kg per day and in females at all T3 doses. Concurrent dronedarone prevented T3 effects in males on the NSFT and in the TST and FST in both genders. Attenuation of 8-OH-DPAT-induced hypothermia was observed in males only and may be reduced by concurrent dronedarone. These findings support an antidepressant- like effect of T3. Attenuation of 8-OH-DPAT-induced hypothermia in males only suggests the need to evaluate a possible gender disparity in the role of presynaptic 5-HT 1A receptors in T3 antidepressant mechanisms. Blockade by dronedarone of the antidepressant-like effects of T3 suggests that these effects are TRα receptor-mediated.

Original languageEnglish
Pages (from-to)494-502
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume337
Issue number2
DOIs
StatePublished - May 2011
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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