Chronic effects of triiodothyronine in combination with imipramine on 5-HTtransporter, 5-HT1A and 5-HT2A receptors in adult rat brain

Triiodothyronine (T3) has been shown to accelerate and potentiate the clini cal response to tricyclic antidepressant (TCA) treatment in depressive diso rders. The neurobiological mechanism underlying these therapeutic effects o f T3 are still unknown. Since brain serotonin (5-HT) changes have been impl icated in the mode of action of TCA drugs, the effects of a chronic (7 or 2 1 days) administration of imipramine (10 mg/kg/day) and of a low dose of T3 (4 mug/kg/day), given alone or in combination, were investigated on the de nsity of midbrain 5-HT transporters and of hippocampal 5-HT1A and cortical 5-HT2A receptors in adult Wistar rats. Neither single nor combined administ ration of imipramine and T3 for 7 days modified the density of 5-HT transpo rters and of 5-HT1A receptors. On day 21, the combination did not change im ipramine- or T3-induced decrease in 5-HT transporter density whereas it pre vented imipramine-induced increased in 5-HT1A receptor density. Whatever th e treatment duration, imipramin-T3 combination potentiated imipramine-induc ed decrease in 5-HT2A receptor density. On both day 7 and 21, T3 given alon e 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 o ccur at the postsynaptic level of 5-HT neurotransmission after antidepressa nt treatment. (C) 2001 American College of Neuropsychopharmacology. Publish ed by Elsevier Science Inc.