PACAP-38 (P38) is a pleiotropic peptide that exerts multiple peripheral and central actions, including neurotrophic, neuroprotective and anti-inflammatory actions. Previous studies have suggested an improvement of memory in rats that have received a single systemic injection of P38. In a therapeutic perspective, we used an analog, acetyl-[Ala15, Ala20]PACAP-38-propylamide (ALG), to improve both stability and affinity for PAC1 receptors vs. endogen PACAP. We investigated the effect of P38 and ALG on memory consolidation using a spatial novelty detection (SND) task in which rats had to memorize a configuration of objects to identify that, during a test session, a familiar object has been moved to a new location. Rats received an intravenous injection of P38 or ALG after the last training session. In Experiment 1, P38 (30 µg/kg) improved spatial memory consolidation allowing detection of novelty vs. saline injection. In Experiment 2, we confirmed this effect and showed that P38 restored the performance similar to what was found using non-injected rats. This suggests that, contrary to ALG, P38 exerted a promesiant rather than an anxiety-related effect whereas ALG did not show similar action. We also examined whether P38 effect involved an interaction with NR2B-containing NMDA receptors (NMDARs) by administrating ifenprodil (IFE; a selective NR2B-containing NMDAR antagonist) alone or in combination with P38 or ALG. The results suggested that P38 action on memory involved NR2B-containing NMDARs. Lastly, brain-derived neutrophic factor (BDNF) modulation appeared to be not related to the behavioral performance in the SND task. Overall, the results indicate that P38 exerted a beneficial effect on memory consolidation in a non-associative task, whereas ALG did not have this action.

中文翻译：

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PACAP-38 和类似物乙酰基-[Ala15, Ala20] PACAP-38-丙基酰胺对大鼠空间新奇任务检测中记忆巩固的影响。

PACAP-38 (P38) 是一种多效性肽，可发挥多种外周和中枢作用，包括神经营养、神经保护和抗炎作用。先前的研究表明，接受单次全身注射 P38 的大鼠的记忆力有所改善。从治疗的角度来看，我们使用类似物乙酰基-[Ala15, Ala20]PACAP-38-丙基酰胺 (ALG)，以提高对 PAC1 受体与内源性 PACAP 的稳定性和亲和力。我们使用空间新颖性检测 (SND) 任务研究了 P38 和 ALG 对记忆巩固的影响，在该任务中，大鼠必须记住物体的配置，以识别在测试过程中熟悉的物体已被移动到新位置。在最后一次训练后，大鼠接受了 P38 或 ALG 的静脉注射。在实验 1 中，P38 (30 µg/kg) 改进了空间记忆整合，允许检测新奇与盐水注射。在实验 2 中，我们证实了这种效果，并表明 P38 恢复了与使用未注射大鼠发现的相似的性能。这表明，与 ALG 相反，P38 发挥了 promesiant 而不是焦虑相关的作用，而 ALG 没有表现出类似的作用。我们还通过单独给药或与 P38 或 ALG 联合给药艾芬地尔（IFE；选择性含有 NR2B 的 NMDAR 拮抗剂）检查了 P38 效应是否涉及与含有 NR2B 的 NMDA 受体（NMDAR）的相互作用。结果表明，P38 对记忆的作用涉及含有 NR2B 的 NMDAR。最后，脑源性神经营养因子 (BDNF) 调制似乎与 SND 任务中的行为表现无关。总体，