Chronic Effects of Triiodothyronine in Combination with Imipramine on 5-HT Transporter, 5-HT1A and 5-HT2A Receptors in Adult Rat Brain

Triiodothyronine (T3) has been shown to accelerate and potentiate the clinical response to tricyclic antidepressant (TCA) treatment in depressive disorders. The neurobiological mechanisms underlying these therapeutic effects of T3 are still unknown. Since brain serotonin (5-HT) changes have been implicated in the mode of action of TCA drugs, the effects of a chronic (7 or 21 days) administration of imipramine (10 mg/kg/day) and of a low dose of T3 (4 μg/kg/day), given alone or in combination, were investigated on the density of midbrain 5-HT transporters and of hippocampal 5-HT1A and cortical 5-HT2A receptors in adult Wistar rats. Neither single nor combined administration of imipramine and T3 for 7 days modified the density of 5-HT transporters and of 5-HT1A receptors. On day 21, the combination did not change imipramine- or T3-induced decrease in 5-HT transporter density whereas it prevented imipramine-induced increase in 5-HT1A receptor density. Whatever the treatment duration, imipramine-T3 combination potentiated imipramine-induced decrease in 5-HT2A receptor density. On both day 7 and day 21, T3 given alone had no effects on the density of 5-HT1A and 5-HT2A receptors. These data indicate that T3 is able to modulate the long-term adaptive changes which occur at the postsynaptic level of 5-HT neurotransmission after antidepressant treatment.