Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Int J Neuropsychopharmacol. 2011 Aug;14(7):967-76. doi: 10.1017/S1461145710001276. Epub 2010 Nov 3.
The dentate gyrus (DG), a part of the hippocampal formation, is a candidate target of antidepressants and may play a role in the development of depressive syndrome; however, there is no direct neurobiological evidence supporting this theory. Here, we examined whether DG integrity is necessary for the behavioural effects of acute or chronic antidepressant treatment. Microinjection of colchicine into DG severely damaged the granule cells, as confirmed by morphological, electrophysiological, and behavioural analyses. Acute treatment with desipramine and fluoxetine decreased the immobility of saline-treated rats in the forced swimming test, whereas this decrease was inhibited in colchicine-treated rats. Chronic treatment with desipramine and fluoxetine also decreased the immobility of saline-treated rats; however, the extensive DG damage induced by colchicine had no effect on this decrease. In the novelty-suppressed feeding test, chronic treatment with desipramine and fluoxetine decreased the latency to feed in saline-treated rats while, once again, the extensive DG damage caused by colchicine had no effect on this decrease. Thus, we concluded that DG integrity was required for the behavioural effects of acute but not chronic antidepressant treatment; this disparity was not due to the time interval between surgery and behavioural tests. These findings indicate that treatment duration determines the influence of DG integrity on antidepressant effects.
齿状回（DG）是海马结构的一部分，是抗抑郁药的候选靶点，可能在抑郁综合征的发展中起作用；然而，目前没有直接的神经生物学证据支持这一理论。在这里，我们研究了 DG 完整性是否对抗抑郁药急性或慢性治疗的行为效应是必需的。用秋水仙碱微注射 DG 会严重损害颗粒细胞，这通过形态学、电生理学和行为分析得到了证实。急性用去甲丙咪嗪和氟西汀处理会减少盐水处理大鼠在强迫游泳试验中的不动性，而这种减少在秋水仙碱处理的大鼠中被抑制。慢性用去甲丙咪嗪和氟西汀处理也会减少盐水处理大鼠的不动性；然而，秋水仙碱引起的广泛 DG 损伤对这种减少没有影响。在新奇抑制进食试验中，慢性用去甲丙咪嗪和氟西汀处理会减少盐水处理大鼠的进食潜伏期，而秋水仙碱引起的广泛 DG 损伤对这种减少也没有影响。因此，我们得出结论，DG 完整性对抗抑郁药急性治疗的行为效应是必需的，但对慢性治疗的行为效应则不是必需的；这种差异不是由于手术和行为测试之间的时间间隔造成的。这些发现表明，治疗持续时间决定了 DG 完整性对抗抑郁药效果的影响。
