TY - JOUR T1 - Effect of Triiodothyronine on Antidepressant Screening Tests in Mice and on Presynaptic 5-HT<sub>1A</sub> Receptors: Mediation by Thyroid Hormone α Receptors JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 494 LP - 502 DO - 10.1124/jpet.111.179564 VL - 337 IS - 2 AU - T. Lifschytz AU - P. Zozulinsky AU - R. Eitan AU - G. Landshut AU - S. Ohayon AU - B. Lerer Y1 - 2011/05/01 UR - http://jpet.aspetjournals.org/content/337/2/494.abstract N2 - 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 antidepressant-like 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-HT1A receptors in the antidepressant-like mechanism of T3 by the hypothermic response to the 5-HT1A 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 combination 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 &gt;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-HT1A receptors in T3 antidepressant mechanisms. Blockade by dronedarone of the antidepressant-like effects of T3 suggests that these effects are TRα receptor-mediated. ER -