Mechanisms of treatment-resistant depression on the basic study of hippocampal neurogenesis in ACTH-treated rats

在用促肾上腺皮质激素(ACTH)治疗的大鼠的强迫游泳试验中，我们检测了它对不动时间的影响。多巴胺再摄取抑制剂安非他酮和D2/D3受体激动剂普拉克索显著缩短正常和ACTH治疗大鼠的不动时间。伏隔核内注入安非他酮和普拉克索，但不注射内侧前额叶皮质，可降低正常大鼠和ACTH治疗大鼠在强迫游泳试验中的不动。这些发现表明，安非他酮和普拉克索的抗抑郁作用与大鼠伏隔核中的多巴胺水平有关。我们先前报道，长期给予ACTH显著减少了海马齿状回颗粒下带BrdU阳性细胞的数量。在ACTH处理的大鼠中，这种作用被丙咪嗪和锂的联合给药以及电惊厥刺激14天所逆转。这些结果支持丙咪嗪和锂，以及电惊厥刺激将通过触发细胞增殖来提高难治性抑郁症的治疗效果的观点。

We examined its influence on the duration of immobility during the forced swim test in adrenocorticotropic hormone(ACTH)-treated rats. The dopamine reuptake inhibitor bupropion and D2/D3 receptor agonist pramipexole significantly decreased the duration of immobility in normal and ACTH-treated rats. The infusions of bupropion and pramipexole into the nucleus accumbens, but not medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. These findings suggest the antidepressant-like effect of bupropion and pramipexole to be related to levels of dopamine in the rat nucleus accumbens.We previously reported that the chronic administration of ACTH significantly decreased the number of BrdU-positive cells in the subgranular zone of the hippocampal dentate gyrus. This effect was reversed by the coadministration of imipramine and lithium, and electroconvulsive stimuli for 14 days in ACTH-treated rats. These results support the notion that imipramine and lithium, and electroconvulsive stimuli would improve the efficacy of treatment for resistant depression by triggering cell proliferation.