The present report examines the effects of repeated or single intrahippocampal Reelin infusions on measures of depressive-like behavior, cognition, and hippocampal neurogenesis in the repeated-corticosterone (CORT) paradigm. Rats received subcutaneous injections of CORT for 3 weeks and Reelin was infused through an inserted canula in the left hippocampus on days 7, 14, and 21, or only on day 21 of CORT injections. CORT increased immobility in the forced-swim test and impaired object-location memory. Notably, these effects were reversed by both repeated and single-Reelin infusions. CORT decreased both the number and complexity of doublecortin-labeled maturing newborn neurons in the dentate gyrus subgranular zone, and a single-Reelin infusion increased the number but not complexity of newborn neurons, while repeated Reelin infusions restored both. Injection of the AMPA antagonist CNQX blocked the rescue of the behavioral phenotype by Reelin but did completely block the effects of Reelin on hippocampal neurogenesis. Reelin is able to rescue the deficits in AMPA, NMDA, GABAA receptors, mTOR and p-mTOR induced by CORT. These novel results demonstrate that a single intrahippocampal Reelin infusion into the dorsal hippocampus has fast-acting antidepressant-like effects, and that some of these effects may be at least partially independent of Reelin actions on hippocampal neurogenesis.

中文翻译：

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在重复皮质酮慢性应激范例中评估了 Reelin 的速效抗抑郁样作用。

本报告探讨了重复皮质酮 (CORT) 范式中重复或单次海马内 Reelin 输注对抑郁样行为、认知和海马神经发生的影响。大鼠皮下注射 CORT 3 周，并在第 7、14 和 21 天或仅在 CORT 注射的第 21 天通过左侧海马插入的插管输注 Reelin。CORT 增加了强迫游泳测试中的不动性，并损害了物体位置记忆。值得注意的是，重复和单次 Reelin 输注都可以逆转这些效应。CORT 降低了齿状回颗粒下区双皮质素标记的成熟新生神经元的数量和复杂性，单次 Reelin 输注增加了新生神经元的数量，但没有增加新生神经元的复杂性，而重复 Reelin 输注则恢复了两者。注射 AMPA 拮抗剂 CNQX 阻断了 Reelin 对行为表型的挽救，但确实完全阻断了 Reelin 对海马神经发生的影响。Reelin 能够挽救 CORT 诱导的 AMPA、NMDA、GABAA 受体、mTOR 和 p-mTOR 缺陷。这些新颖的结果表明，单次海马内 Reelin 输注到背侧海马具有快速起效的抗抑郁样作用，并且其中一些作用可能至少部分独立于 Reelin 对海马神经发生的作用。