摘要Objectives:Recent findings have further highlighted the role of the thyroid system in the pathophysiology of depression and revealed new physiologically relevant elements of the thyroid system. Our previous study showed an antidepressant-like effect of 3,5-diiodo-L-thyronine (T2), which was previously considered to be a physiologically inactive molecule, in mice. Here, we aimed to investigate the antidepressant-like effects of T2 further. <br> Methods:We studied the effects of bolus injections of T2 to C57Bl6J mice at doses of 0.25 or 0.75 mg/kg with the tail suspension and forced swim models. The effects of the higher dose were investigated in CD1 mice in the forced swim test. Potential behavioral effects of these treatments were also studied using the novel cage and dark-light box tests. Results:A reduction of depressive-like behavior was found in mice treated with 0.75 mg/kg of T2 in the tail suspension test, but not in the forced swim test. Locomotion and anxiety variables were unaltered following treatment with T2. There were no significant changes after bolus administration of 0.25 mg/kg T2 in either test for depressive-like behavior. Thus, bolus injection of T2 at the dose 0.75 mg/kg can induce antidepressant-like effects without affecting other behaviors. <br> Conclusions:A discrepant result in the forced swim test may be due to its different sensitivity to T2 compared with the tail suspension paradigm. Furthermore, the development of procedural modifications of this model can be useful in its application in pre-clinical studies.