The nociceptin system and hippocampal cognition in mice A pharmacological and genetic analysis
The nociceptin system and hippocampal cognition in mice A pharmacological and genetic analysis
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DOI：
10.1016/j.brainres.2009.09.075
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发表时间：
2009-12-11
期刊：
影响因子：
2.9
通讯作者：
Ogren, Sven Ove
中科院分区：
文献类型：
--
作者：
Kuzmin, Alexander;Madjid, Nather;Ogren, Sven Ove
本研究利用水迷宫检验了 NOP 激动剂伤害感受肽/孤啡肽 FQ (N/OFQ) 和 Ro 64-6198、NOP 拮抗剂 [Nphe(1)]N/OFQ(1-13)-NH2 Nphe(1) 和纳洛酮苯甲酰腙 (NalBzoH) 对 NMRI 小鼠和原伤害感受肽 (proNC) 敲除 (KO) 小鼠空间记忆的影响任务。 N/OFQ 静脉注射给药（1、5 和 10 nmol/小鼠）和海马 CA3（1 nmol/小鼠，双侧），迷宫中的获取和保留受损。通过 Nphe(1)（10 nmol，i.c.v..）预处理来阻断损伤。 Ro 64-6198 (0.1-0.3-1 mg/kg i.p.)也会剂量依赖性地损害学习能力。然而，用 NalBzoH（1 mg/kg，S.C.）预处理未能改变 Ro 64-6198 的效果。 Nphe(1)（10 nmol/小鼠 i.c.v.）和 NalBzoH（1 mg/kg，S.C.）本身并未影响迷宫性能，尽管有增强性能的趋势。 Prepro N/OFQ 敲除 (ppN/OFQ-/-) 显示出学习能力改善的证据，这在保留试验和逆转训练中很明显。 ppN/OFQ -/- 小鼠在任务中未受到 N/OFQ（10 nmol i.c.v.）的损害，表明突触后 NOP 受体可能发生在此类 KO 小鼠中。结论是，N/OFQ 和 NOP 受体可能通过调节谷氨酸能功能，在海马依赖性空间学习和记忆中发挥重要作用。 (C) 2009 Elsevier B.V. 保留所有权利。
This study examines the effects of NOP agonists nociceptin/orphanin FQ (N/OFQ) and Ro 64-6198, NOP antagonists [Nphe(1)]N/OFQ(1-13)-NH2 Nphe(1) and naloxone benzoylhydrazone (NalBzoH) on spatial memory in NMRI mice and pronociceptin (proNC) knockout (KO) mice using the water maze task. N/OFQ administered i.c.v. (1, 5 and 10 nmol/mouse) and into hippocampal CA3 (1 nmol/mouse, bilaterally), impaired acquisition and retention in the maze. Impairments were blocked by pre-treatment with Nphe(1) (10 nmol, i.c.v..). Ro 64-6198 (0.1-0.3-1 mg/kg i.p.) also dose-dependently impaired learning. However, pre-treatment with NalBzoH (1 mg/kg, S.C.) failed to modify the effects of Ro 64-6198. Nphe(1)(10 nmol/mouse i.c.v.) and NalBzoH (1 mg/kg, S.C.) by themselves failed to affect maze performance, despite a tendency for enhanced performance. Prepro N/OFQ knockout (ppN/OFQ-/-) showed evidence of improved learning, evident at retention trials and in reversal training. ppN/OFQ -/- mice were not impaired by N/OFQ (10 nmol i.c.v.) in the task, suggesting that changes in postsynaptic NOP receptors may occur in such KO mice. It is concluded that N/OFQ and NOP receptors have an important role in hippocampus-dependent spatial learning and memory, probably by modulation of glutamatergic functions. (C) 2009 Elsevier B.V. All rights reserved.