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血管加压素片段类似物NC - 1900预训练给药对非失忆或二氧化碳致失忆小鼠记忆表现的影响。

Effect of pretraining administration of NC-1900, a vasopressin fragment analog, on memory performance in non- or CO2-amnesic mice.

作者信息

Sato Tomoaki, Tanaka Koh-ichi, Teramoto Toyonori, Ohnishi Yoshiko, Hirate Kenji, Irifune Masahiro, Nishikawa Takashige

机构信息

Department of Applied Pharmacology, Kagoshima University Graduate School of Medical & Dental Sciences, Sakuragaoka-8, Kagoshima 890-8544, Japan.

出版信息

Pharmacol Biochem Behav. 2004 Jun;78(2):309-17. doi: 10.1016/j.pbb.2004.04.002.

Abstract

In the present study, we investigated the facilitative effect of NC-1900, a new arginine vasopressin (AVP(1-9)) fragment analog, on memory performance in eight-arm radial maze or passive avoidance (PA) tasks in nonamnesic and amnesic (PA tasks only) mice. In the radial maze, all injections (subcutaneous) were given daily 60 min before each trail. NC-1900 (1 ng/kg)-treated animals showed enhancement of performance, and AVP(4-9) (1 microg/kg), an AVP(1-9) fragment, had similar effects, although the effective dose was 1000-fold higher. In the PA task, all drugs were administrated subcutaneously 60 min before the acquisition trial (Acq.), and the amnesic mice were exposed to CO(2) just after the Acq. NC-1900 (1 ng/kg) enhanced the memory performance of nonamnesic mice and ameliorated CO(2)-induced amnesia. AVP(4-9) (1 microg/kg) had a similar effect, although only at higher doses, while AVP(1-9) (0.1-1 microg/kg) had no effect. The facilitating effect of NC-1900 on nonamnesic mice was inhibited by coinjection [Pmp(1)-Tyr(Me)(2)]-AVP (Pmp,Tyr-AVP; 1 microg/kg), a V(1A) antagonist, but not by OPC-31260, a vasopressin(2) (V(2)) antagonist. The effect of NC-1900 on CO(2)-induced amnesia was also decreased by coinjection of Pmp,Tyr-AVP or [deamino-Pen(1), Me-Tyr(2)]-AVP (10 microg/kg), both of which are V(1) antagonists. These results suggested that NC-1900 has a more potent effect on facilitation of memory via the V(1A) receptor than AVP(4-9) in non- and CO(2)-amnesic conditions.

摘要

在本研究中,我们调查了新型精氨酸加压素(AVP(1-9))片段类似物NC-1900对非失忆小鼠和失忆小鼠(仅针对被动回避任务)在八臂放射状迷宫或被动回避(PA)任务中的记忆表现的促进作用。在放射状迷宫中,所有注射(皮下注射)均在每天每次试验前60分钟进行。接受NC-1900(1纳克/千克)处理的动物表现得到增强,AVP(1-9)片段AVP(4-9)(1微克/千克)也有类似效果,尽管有效剂量高出1000倍。在PA任务中,所有药物均在获取试验(Acq.)前60分钟皮下注射,失忆小鼠在Acq.后立即暴露于CO₂。NC-1900(1纳克/千克)增强了非失忆小鼠的记忆表现,并改善了CO₂诱导的失忆。AVP(4-9)(1微克/千克)有类似效果,不过仅在更高剂量时,而AVP(1-9)(0.1 - 1微克/千克)则无效果。NC-19对非失忆小鼠的促进作用被共注射V(1A)拮抗剂[Pmp(1)-Tyr(Me)(2)]-AVP(Pmp,Tyr-AVP;1微克/千克)抑制,但未被加压素(2)(V(2))拮抗剂OPC-31260抑制。共注射Pmp,Tyr-AVP或[脱氨基-Pen(1), Me-Tyr(2)]-AVP(10微克/千克)(两者均为V(1)拮抗剂)也降低了NC-1900对CO₂诱导失忆的作用。这些结果表明,在非失忆和CO₂诱导失忆的条件下,NC-1900通过V(1A)受体对记忆促进的作用比AVP(4-9)更强。

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