Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
Prog Neuropsychopharmacol Biol Psychiatry. 2010 May 30;34(4):632-8. doi: 10.1016/j.pnpbp.2010.02.029. Epub 2010 Mar 4.
Thyroid hormones, particularly triiodothyronine (T3), have long been used for the treatment of depression, most frequently to enhance the therapeutic activity of other antidepressants. The purpose of this study was to evaluate possible underlying mechanisms for the antidepressant activity of T3. The effects of T3 20 microg/kg/d S.C. and fluoxetine 5mg/kg/d I.P. given alone or in combination for 7 days on the transcription rates of inhibitory serotonergic receptors (5-HT1A and 5-HT1B) were studied in different brain areas of male Sabra rats using real-time PCR. Significant effects of fluoxetine were found on the expression of 5-HT1B receptors in the frontal cortex and of T3 on the expression of 5-HT1A receptors in the amygdala and hippocampus and 5-HT1B receptors in the frontal and entorhinal cortices, the expression being reduced in all cases. An effect of the combination of T3 plus fluoxetine to reduce transcription was observed for 5-HT1A receptors, in the amygdala and dentate gyrus and for 5-HT1B receptors in the entorhinal cortex and anterior raphe nucleus. In the second experiment, the novelty suppressed feeding test (NFST) was used to examine the effects of fluoxetine 5mg/kg/d I.P. and T3 20 or 50 microg/kg/d, alone or in combination for 12 days, on latency to feed. Only the combinations of T3 (20 or 50 microg/kg/d) and fluoxetine (5mg/kg/d) yielded significant behavioral effects in this test. The results of our studies suggest that the mechanism underlying the antidepressant effect of T3 may involve a reduction in 5-HT1A and 5-HT1B receptor transcription rates.
甲状腺激素，特别是三碘甲状腺原氨酸（T3），长期以来一直被用于治疗抑郁症，最常用于增强其他抗抑郁药的治疗活性。本研究的目的是评估 T3 抗抑郁活性的潜在机制。使用实时 PCR 研究了 T3 20μg/kg/d sc 和氟西汀 5mg/kg/d ip 单独或联合给药 7 天对雄性 Sabra 大鼠不同脑区抑制性 5-羟色胺能受体（5-HT1A 和 5-HT1B）转录率的影响。发现氟西汀对前额叶皮层中 5-HT1B 受体的表达有显著影响，T3 对杏仁核和海马中 5-HT1A 受体的表达和前额叶和内嗅皮质中 5-HT1B 受体的表达有显著影响，所有情况下的表达均减少。观察到 T3 加氟西汀联合减少转录的效应，用于 5-HT1A 受体，在杏仁核和齿状回，以及 5-HT1B 受体，在内嗅皮质和前中缝核。在第二个实验中，使用新颖性抑制进食测试（NFST）来检查氟西汀 5mg/kg/d ip 和 T3 20 或 50μg/kg/d，单独或联合给药 12 天，对进食潜伏期的影响。只有 T3（20 或 50μg/kg/d）和氟西汀（5mg/kg/d）的组合在该测试中产生了显著的行为效应。我们的研究结果表明，T3 抗抑郁作用的机制可能涉及减少 5-HT1A 和 5-HT1B 受体转录率。
