Flood J F, Garland J S, Morley J E
St. Louis University, Division of Geriatric Medicine, MO 63104.
Peptides. 1990 Sep-Oct;11(5):933-8. doi: 10.1016/0196-9781(90)90012-t.
Vasoactive intestinal peptide (VIP) is a neuropeptide present in high concentrations in the hippocampus. The studies reported here demonstrate that VIP administered into the third ventricle of the brain caused amnesia in mice trained on a left-right footshock avoidance task in a T-maze. VIP resulted in amnesia when administered directly into the rostral portion of the hippocampus at a 10-fold lower dose than was needed to produce amnesia when VIP was administered intracerebroventricularly. When VIP was administered 24 hr after training, it failed to impair retention measured a week later. VIP receptor antagonist ([4-Cl-D-Phe6,Leu17]VIP) enhanced retention when administered into the rostral portion of the hippocampus, suggesting that VIP plays a physiological role in memory modulation. VIP receptor antagonist administered 24 hr after training did not facilitate retention. To gain some insight as to how VIP may be affecting memory processing, we determined if some memory-improving compounds showed a selective ability to block amnesia induced by VIP. The amnestic effect of VIP was blocked by peripheral administration of the memory-enhancing agents, arecoline, naloxone and ST 587 (a noradrenergic receptor agonist) but not by cholecystokinin octapeptide. Central administration of arecoline, but not neuropeptide Y, blocked the amnestic effect of VIP. It is concluded that VIP is a potent amnestic peptide.
血管活性肠肽（VIP）是一种在海马体中高浓度存在的神经肽。此处报道的研究表明，将VIP注入脑的第三脑室会使在T迷宫中接受左右足部电击回避任务训练的小鼠出现失忆。当以比脑室内注射产生失忆所需剂量低10倍的剂量直接将VIP注入海马体的嘴侧部分时，也会导致失忆。当在训练后24小时给予VIP时，它不会损害一周后测得的记忆保持。VIP受体拮抗剂（[4-氯-D-苯丙氨酸6，亮氨酸17]VIP）注入海马体嘴侧部分时会增强记忆保持，这表明VIP在记忆调节中发挥生理作用。训练后24小时给予VIP受体拮抗剂并不会促进记忆保持。为了深入了解VIP可能如何影响记忆处理，我们确定了一些改善记忆的化合物是否具有选择性阻断VIP诱导失忆的能力。VIP的失忆作用可被记忆增强剂槟榔碱、纳洛酮和ST 587（一种去甲肾上腺素能受体激动剂）的外周给药阻断，但不能被八肽胆囊收缩素阻断。槟榔碱的中枢给药而非神经肽Y阻断了VIP的失忆作用。结论是VIP是一种强效的失忆肽。
