Effects of a neurotensin analogue (PD149163) and antagonist (SR142948A) on the scopolamine-induced deficits in a novel object discrimination task
Effects of a neurotensin analogue (PD149163) and antagonist (SR142948A) on the scopolamine-induced deficits in a novel object discrimination task
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DOI：
10.1097/01.fbp.0000224382.63744.20
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发表时间：
2006-06-01
影响因子：
1.6
通讯作者：
Bennett, Geoffrey W.
中科院分区：
文献类型：
--
作者：
Azmi, Norazrina;Norman, Christine;Bennett, Geoffrey W.
各种证据表明，内源性神经肽神经降压素在认知中的作用，涉及与中枢神经系统胆碱能途径的相互作用。初步研究表明，在东莨菪碱（一种可诱导记忆缺陷的毒蕈碱受体拮抗剂）存在下，神经降压素的中枢给药可增强空间和非空间工作记忆。利用类似的方法，本研究采用了两个试验新的对象的歧视任务，以确定急性影响的神经降压肽类似物与改善代谢稳定性，PD 149163，识别记忆李斯特兜帽大鼠。与以前的神经降压素的研究结果一致，接受侧脑室注射PD 149163（3 μ g）的动物在选择试验期间显著区分了新的熟悉对象。此外，类似剂量的PD 149163恢复了东莨菪碱诱导的新奇识别缺陷。SR 142948 A（一种非选择性神经降压素受体拮抗剂）在1 mg/kg（腹膜内）剂量下可阻断PD 149163对东莨菪碱诱导的遗忘的恢复作用，但在0.1 mg/kg剂量下则不能阻断。总之，本研究结果证实了神经降压素在介导记忆过程中的作用，可能通过中枢胆碱能机制。
Various lines of evidence suggest a role in cognition for the endogenous neuropeptide, neurotensin, involving an interaction with the central nervous system cholinergic pathways. A preliminary study has shown that central administration of neurotensin enhances spatial and nonspatial working memory in the presence of scopolamine, a muscarinic receptor antagonist which induces memory deficits. Utilizing similar methods, the present study employed a two-trial novel object discrimination task to determine the acute effect of a neurotensin peptide analogue with improved metabolic stability, PD149163, on recognition memory in Lister hooded rats. Consistent with previous findings with neurotensin, animals receiving an intracerebroventricular injection of PD149163 (3 mu g) significantly discriminated the novel from familiar object during the choice trial. In addition, a similar dose of PD149163 restored the scopolamine-induced deficit in novelty recognition. The restoration effect on scopolamine-induced amnesia produced by PD149163 was blocked by SR142948A, a nonselective neurotensin receptor antagonist, at a dose of 1 mg/kg (intraperitonial) but not at 0.1 mg/kg. In conclusion, the present results confirm a role for neurotensin in mediating memory processes, possibly via central cholinergic mechanisms.