Triiodothyroacetic acid-induced reversal of learned helplessness in rats

Triiodothyronine (T3), successfully used as therapeutic agent in euthyroid depressive states, has been found to exert an antidepressant-like effect in various psychopharmacological tests in rodents. Therefore the possible antidepressant-like activity of triiodothyroacetic acid (TA3), a natural metabolite of T3, was investigated in rats subjected to helplessness training. The animals were first exposed to inescapable shock pretreatment (60 shocks, 15 s duration, 0.8 mA every min +/- 15 s) and 48 h later, shuttle-box training (30 trials/day, ITI: 30 s) was performed on 3 consecutive days in order to assess escape deficits. As compared to control rats (no shock pretreatment), the rats exposed to inescapable shocks exhibited escape deficits when tested for subsequent responding in the shuttle-box. Daily i.p. injections of TA3 (0.5 mg/kg) prevented escape deficits as did daily injections of tricyclic antidepressants. These data are in agreement with previous results bearing on the similarity of action of TA3 and tricyclic antidepressants and extend to the thyroid axis the neuroendocrine systems that can be affected by exposure to uncontrollable stressors.