Hayashi Hiromi, Doi Maho, Onoue Yuka, Kuwatsuka Keiko, Miyake Ayaka, Koyama Toshihiro, Shinomiya Kazuaki, Miyazaki Ikuko, Aasanuma Masato, Kitamura Yoshihisa
Department of Pharmaceutical Care and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Yakugaku Zasshi. 2012;132(2):173-8. doi: 10.1248/yakushi.132.173.
We previously reported that adrenocorticotropic hormone (ACTH)-treated rats serve as a valuable animal model for tricyclic antidepressant-resistant depressive conditions. The present study was undertaken to investigate the changes in neurogenesis in the hippocampus of ACTH-treated rats. Chronic treatment of ACTH decreased the number of bromodeoxyuridine-labeled cells in the dentate gyrus, and the coadministration of imipramine and lithium, and electroconvulsive stimuli recovered these reductions. Furthermore, chronic ACTH treatment also decreased the expression of brain-derived neurotrophic factor, and the coadministration of imipramine and lithium, and electroconvulsive stimuli recovered these reductions. These results suggest that antidepressant-resistant depression is caused by the suppression of neurogenesis, and the coadministration of imipramine and lithium, and electroconvulsive stimuli exert an antidepressant-like effect by recovering proliferative signals and neurogenesis.
我们之前报道过，促肾上腺皮质激素（ACTH）处理的大鼠可作为三环类抗抑郁药耐药性抑郁状态的有价值动物模型。本研究旨在调查ACTH处理大鼠海马体中神经发生的变化。ACTH的慢性处理减少了齿状回中溴脱氧尿苷标记细胞的数量，而丙咪嗪和锂的联合给药以及电惊厥刺激可恢复这些减少的数量。此外，ACTH的慢性处理还降低了脑源性神经营养因子的表达，丙咪嗪和锂的联合给药以及电惊厥刺激可恢复这些降低的表达。这些结果表明，抗抑郁药耐药性抑郁症是由神经发生的抑制引起的，丙咪嗪和锂的联合给药以及电惊厥刺激通过恢复增殖信号和神经发生发挥抗抑郁样作用。
