Department of Psychiatry Columbia University/New York State Psychiatric Institute , New York, NY , USA.
World J Biol Psychiatry. 2013 Dec;14(8):602-10. doi: 10.3109/15622975.2013.768356. Epub 2013 Feb 11.
Although hippocampal neurogenesis has been implicated in mood disorders, the precise role new neurons play in mood regulation is not fully elucidated. Here we examine whether neurogenesis improves mood by facilitating segregation of novel experiences that conflict with older maladaptive memories.
Study 1: Four groups (N = 9 each) of adult male rats (exposed to stress or control conditions plus antidepressant or placebo) underwent active training on the place-avoidance task (PAT) on week 0; tested on recalling the "Initial PAT" on weeks 4 and 8; learning a subtly "Altered PAT" on week 8; and euthanazed on week 9. Study-2: Two groups (N = 12 each) rats tested either on the Initial-PAT or Altered-PAT 3 days post-training and immediately euthanized.
Stressed subjects treated with placebo were slower in learning the week 8 Altered Task and had lower neurogenesis rates than non-stressed animals and Stressed subjects given drug (Study 1). Synaptic activation of mature hippocampal neurons inversely correlated with Altered-PAT performance and with neurogenesis rates (Study 2).
Increasing neurogenesis enhances acquisition of novel experiences possibly by suppressing activation of mature hippocampal neurons that mediate established, conflicting memories. Therefore, antidepressants may improve mood by stimulating new hippocampal neurogenesis that facilitate detection of positive experiences while suppressing interference from recurring depressogenic thought patterns.
尽管海马神经发生与情绪障碍有关，但新神经元在情绪调节中的确切作用尚未完全阐明。在这里，我们研究了神经发生是否通过促进与旧适应不良记忆冲突的新体验的分离来改善情绪。
研究 1：四组成年雄性大鼠（暴露于应激或对照条件下，加用抗抑郁药或安慰剂）在第 0 周进行位置回避任务（PAT）的主动训练；在第 4 周和第 8 周测试回忆“初始 PAT”；在第 8 周学习微妙的“改变的 PAT”；并在第 9 周安乐死。研究 2：两组大鼠（每组 12 只）在训练后 3 天接受初始 PAT 或改变的 PAT 测试，并立即安乐死。
接受安慰剂治疗的应激大鼠在第 8 周的改变任务中学习速度较慢，神经发生率低于非应激动物和给予药物的应激大鼠（研究 1）。成熟海马神经元的突触激活与改变的 PAT 表现和神经发生率呈负相关（研究 2）。
增加神经发生可能通过抑制成熟海马神经元的激活来增强新体验的获得，成熟海马神经元介导已建立的、冲突的记忆。因此，抗抑郁药可能通过刺激新的海马神经发生来改善情绪，从而促进对积极体验的检测，同时抑制反复出现的致抑郁思维模式的干扰。
