title: Effect of triiodothyronine on antidepressant screening tests in mice and on presynaptic 5-HT1A receptors: mediation by thyroid hormone α receptors.
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 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-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 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 >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.
authors.affiliation: Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Lifschytz
authors.forename: P
authors.initials: P
authors.lastname: Zozulinsky
authors.forename: R
authors.initials: R
authors.lastname: Eitan
authors.forename: G
authors.initials: G
authors.lastname: Landshut
authors.forename: S
authors.initials: S
authors.lastname: Ohayon
authors.forename: B
authors.initials: B
authors.lastname: Lerer
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000638:Amiodarone / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000077764:Dronedarone; D004353:Drug Evaluation, Preclinical; D004777:Environment; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D019417:Hindlimb Suspension / Q000523:psychology; D007035:Hypothermia / Q000139:chemically induced; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D017661:Receptors, Presynaptic; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012727:Sex Characteristics; D013550:Swimming / Q000523:psychology; D037021:Thyroid Hormone Receptors alpha / Q000187:drug effects*; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D017661:Receptors, Presynaptic; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D037021:Thyroid Hormone Receptors alpha; D014284:Triiodothyronine; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000077764:Dronedarone; D000638:Amiodarone