Chronic effects of triiodothyronine in combination with imipramine on 5-HT transporter, 5-HT(1A) and 5-HT(2A) 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 microg/kg/day), given alone or in combination, were investigated on the density of midbrain 5-HT transporters and of hippocampal 5-HT(1A) and cortical 5-HT(2A) 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-HT(1A) 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-HT(1A) receptor density. Whatever the treatment duration, imipramine-T3 combination potentiated imipramine-induced decrease in 5-HT(2A) receptor density. On both day 7 and day 21, T3 given alone had no effects on the density of 5-HT(1A) and 5-HT(2A) 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.
Moreau
X
X
INSERM U501, Faculté de Médecine Nord, Marseille, France.
Jeanningros
R
R
Mazzola-Pomietto
P
P
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000493:pharmacokinetics; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000493:pharmacokinetics*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D015283:Citalopram / Q000493:pharmacokinetics; D003866:Depressive Disorder / Q000378:metabolism / Q000503:physiopathology; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D007099:Imipramine / Q000097:blood / Q000493:pharmacokinetics*; D007650:Ketanserin / Q000493:pharmacokinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000378:metabolism; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014284:Triiodothyronine / Q000097:blood / Q000493:pharmacokinetics*
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000929:Antidepressive Agents, Tricyclic; D002352:Carrier Proteins; D015283:Citalopram; D007099:Imipramine; D007650:Ketanserin; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D014284:Triiodothyronine; C493232:Slc6a4 protein, rat