Wu Xuefei, Castrén Eero
Neuroscience Center, University of Helsinki, Helsinki, Finland.
Biol Psychiatry. 2009 Jul 1;66(1):5-8. doi: 10.1016/j.biopsych.2009.01.023. Epub 2009 Feb 28.
Selective serotonin reuptake inhibitors (SSRI) often produce increased anxiety during the first weeks of treatment before the clinical antidepressant response, and these symptoms are commonly treated with benzodiazepines. Selective serotonin reuptake inhibitors increase proliferation of neuronal progenitors in rodent hippocampus after a delay of approximately 2 weeks.
We have used this delayed increase in neurogenesis, as detected with both a rapid dot-blot method and with immunostaining, as a model of the delayed clinical antidepressant effects.
Whereas the SSRI fluoxetine alone significantly increased both neurogenesis and survival of newborn cells when administered for 2-3 weeks, co-treatment with diazepam and fluoxetine completely blocked the increase in both neurogenesis and survival. Furthermore, neurogenesis was not increased when fluoxetine and diazepam were first co-administered for 2 weeks and then fluoxetine was given alone for 2 additional weeks. Moreover, we show that daily administration is necessary for neurogenesis, because injection of fluoxetine for up to 1 week failed to increase neurogenesis, when assayed at 14 days from the first injection.
These results suggest that benzodiazepines might interfere with the clinical effects of fluoxetine or that increased neurogenesis is not a valid model for the delayed onset of the clinical antidepressant effects.
选择性5-羟色胺再摄取抑制剂（SSRI）在临床抗抑郁反应出现之前的治疗最初几周常常会导致焦虑增加，这些症状通常用苯二氮䓬类药物治疗。选择性5-羟色胺再摄取抑制剂在延迟约2周后会增加啮齿动物海马体中神经祖细胞的增殖。
我们利用这种通过快速斑点印迹法和免疫染色检测到的神经发生延迟增加，作为延迟临床抗抑郁作用的模型。
当单独给予SSRI氟西汀2 - 3周时，其显著增加了神经发生以及新生细胞的存活，但与地西泮和氟西汀联合治疗则完全阻断了神经发生和存活的增加。此外，当氟西汀和地西泮先联合给药2周，然后单独给予氟西汀额外2周时，神经发生并未增加。而且，我们表明神经发生需要每日给药，因为从首次注射起14天时检测发现，注射氟西汀长达1周未能增加神经发生。
这些结果表明苯二氮䓬类药物可能会干扰氟西汀的临床效果，或者增加的神经发生不是临床抗抑郁作用延迟起效的有效模型。
