Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Int J Neuropsychopharmacol. 2010 Jun;13(5):553-61. doi: 10.1017/S1461145709990769. Epub 2009 Oct 19.
The thyroid hormone triiodothyronine (T3) may accelerate and augment the action of antidepressants. Antidepressants up-regulate neurogenesis in adult rodent hippocampus. We studied the effect of T3 and T3+fluoxetine in enhancement of hippocampal neurogenesis beyond that induced by fluoxetine alone and the correlation with antidepressant behaviour in the novelty suppressed feeding test (NSFT). Rats were administered fluoxetine (5 mg/kg.d), T3 (50 mug/kg.d), fluoxetine (5 mg/kg.d)+T3 (50 mug/kg.d) or saline, for 21 d. Neurogenesis was studied by doublecortin (DCX) immunohistochemistry in the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). In the NSFT, latency to feeding in animals deprived of food was measured. Fluoxetine and fluoxetine+T3 increased the number of doublecortin-positive (DCX+) cells in the SGZ compared to saline (p=0.00005, p=0.008, respectively). There was a trend towards an increased number of DCX+ cells by T3 compared to saline (p=0.06). Combined treatment with fluoxetine+T3 further increased the number of DCX+ cells compared to T3 or fluoxetine alone (p=0.001, p=0.014, respectively). There was no effect of any of the treatments on number of DCX+ cells in the SVZ. In the NSFT, all treatments (T3, fluoxetine+T3 and fluoxetine) reduced latency to feeding compared to saline (p=0.0004, p=0.00001, p=0.00009, respectively). Fluoxetine+T3 further reduced latency to feeding compared to T3 alone (p=0.05). The results suggest that enhancement of antidepressant action by T3 may be related to its effect of increasing hippocampal neurogenesis and that the antidepressant effect of these treatments is specific to the hippocampus and does not represent a general effect on cell proliferation.
甲状腺激素三碘甲状腺原氨酸（T3）可能会加速和增强抗抑郁药的作用。抗抑郁药可上调成年啮齿动物海马体中的神经发生。我们研究了 T3 和 T3+氟西汀对单独使用氟西汀诱导的海马神经发生的增强作用，以及与新颖性抑制进食测试（NSFT）中的抗抑郁行为的相关性。大鼠给予氟西汀（5mg/kg.d）、T3（50μg/kg.d）、氟西汀（5mg/kg.d）+T3（50μg/kg.d）或生理盐水，连续 21d。通过双皮质素（DCX）免疫组织化学法研究海马齿状回下区（SGZ）和脑室下区（SVZ）的神经发生。在 NSFT 中，测量动物禁食时的进食潜伏期。与生理盐水相比，氟西汀和氟西汀+T3 增加了 SGZ 中双皮质素阳性（DCX+）细胞的数量（p=0.00005，p=0.008）。与生理盐水相比，T3 有增加 DCX+细胞数量的趋势（p=0.06）。与单独使用 T3 或氟西汀相比，联合使用氟西汀+T3 进一步增加了 DCX+细胞的数量（p=0.001，p=0.014）。任何一种治疗方法对 SVZ 中 DCX+细胞的数量均无影响。在 NSFT 中，所有治疗方法（T3、氟西汀+T3 和氟西汀）均降低了与生理盐水相比的进食潜伏期（p=0.0004、p=0.00001、p=0.00009）。与单独使用 T3 相比，氟西汀+T3 进一步降低了进食潜伏期（p=0.05）。结果表明，T3 增强抗抑郁作用可能与其增加海马神经发生的作用有关，这些治疗方法的抗抑郁作用是针对海马体的，而不是对细胞增殖的一般作用。
